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. Author manuscript; available in PMC: 2018 Feb 20.
Published in final edited form as: Neuroscience. 2016 Dec 3;343:190–212. doi: 10.1016/j.neuroscience.2016.11.036

NEURON-SPECIFIC SUMO KNOCKDOWN SUPPRESSES GLOBAL GENE EXPRESSION RESPONSE AND WORSENS FUNCTIONAL OUTCOME AFTER TRANSIENT FOREBRAIN ISCHEMIA IN MICE

LIN ZHANG a,b, XIAOZHI LIU a,b, HUAXIN SHENG a, SHUAI LIU a, YING LI a,c, JULIA Q ZHAO a, DAVID S WARNER a, WULF PASCHEN a,*, WEI YANG a,*
PMCID: PMC5319602  NIHMSID: NIHMS834002  PMID: 27919694

Abstract

Small ubiquitin-like modifier (SUMO) conjugation (SUMOylation) plays key roles in neurologic function in health and disease. Neuronal SUMOylation is essential for emotionality and cognition, and this pathway is dramatically activated in post-ischemic neurons, a neuroprotective response to ischemia. It is also known from cell culture studies that SUMOylation modulates gene expression. However, it remains unknown how SUMOylation regulates neuronal gene expression in vivo, in the physiologic state and after ischemia, and modulates post-ischemic recovery of neurologic function. To address these important questions, we used a SUMO1-3 knockdown (SUMO-KD) mouse in which a Thy-1 promoter drives expression of 3 distinct microRNAs against SUMO1-3 to silence SUMO expression specifically in neurons. Wild-type and SUMO-KD mice were subjected to transient forebrain ischemia. Microarray analysis was performed in hippocampal CA1 samples, and neurologic function was evaluated. SUMOylation had opposite effects on neuronal gene expression before and after ischemia. In the physiological state, most genes regulated by SUMOylation were up-regulated in SUMO-KD compared to wild-type mice. Brain ischemia/reperfusion significantly modulated the expression levels of more than 400 genes in wild-type mice, with a majority of those genes upregulated. The extent of this post-ischemic transcriptome change was suppressed in SUMO-KD mice. Moreover, SUMO-KD mice exhibited significantly worse functional outcome. This suggests that suppression of global gene expression response in post-ischemic brain due to SUMO knockdown has a negative effect on post-ischemic neurologic function. Together, our data provide a basis for future studies to mechanistically link SUMOylation to neurologic function in health and disease.

Keywords: brain ischemia, SUMO, microarray, knockdown, transgenic mice

INTRODUCTION

Small ubiquitin-like modifier (SUMO) conjugation (SUMOylation) is a post-translational protein modification whereby SUMOs are covalently conjugated to lysine residues in target proteins (Flotho and Melchior, 2013). This is an energy-dependent process that is regulated via the action of activating (E1, ATP-dependent), conjugating (E2), and ligating (E3) enzymes. In mammalian cells, three SUMO isoforms have been identified: SUMO1, SUMO2, and SUMO3. SUMO2 and SUMO3 are highly homologous, and are usually referred to as SUMO2/3. SUMO1, however, shares only about 50% homology with SUMO2/3. Notably, while SUMO1 knockout mice and SUMO3 knockout mice do not show any obvious abnormality, SUMO2 knockout is lethal in the embryonic stage (Evdokimov et al., 2008; Wang et al., 2014b).

SUMOylation can modify the activity, stability, and function of target proteins, and thereby modulate almost all major cellular pathways (Flotho and Melchior, 2013). Our knowledge about the significance of SUMO conjugation in cellular homeostasis is primarily based on results from cell culture experiments. In the physiologic state, most SUMO1 is conjugated to target proteins, predominately the Ran GTPase-activating protein-1 (RanGAP1). Thus, under stress conditions, there is only small change in SUMO1 modification profiles. In contrast, most SUMO2/3 is present as free SUMO in the physiologic state. However, under a variety of stress conditions, including heat, metabolic, and oxidative stress, SUMO2/3 conjugation is dramatically activated (Saitoh and Hinchey, 2000; Yang et al., 2012).

Many of the SUMO targets are nuclear proteins involved in gene expression (Golebiowski et al., 2009; Yang et al., 2014). It has been reported that SUMOylation can both activate and suppress transcription. In most cases, however, gene expression is suppressed when the respective transcription factor is SUMO-conjugated (Gill, 2005; Chymkowitch et al., 2015). The mechanisms that link SUMO conjugation to gene expression are still not fully understood. Generally, experimental studies have focused on individual transcription factors to clarify the role of SUMOylation in expression of target genes. Recently, chromatin immunoprecipitation coupled with next-generation sequencing (ChIP-seq) was used to more completely define these mechanisms (Liu et al., 2012; Neyret-Kahn et al., 2013; Seifert et al., 2015). These studies were carried out in cell cultures. A genome-wide analysis of the effects of SUMOylation on gene expression in vivo has not yet been performed.

SUMO conjugation plays a pivotal role in neurologic function in the physiologic and pathologic state. For example, SUMOylation is essential for emotionality and cognition, and silencing SUMO1-3 expression specifically in neurons impairs episodic and fear memories (Wang et al., 2014a). However, the pathways that link SUMOylation to memory processes have not been identified. Furthermore, SUMOylation is associated with brain ischemia/stroke and degenerative diseases (Yang et al., 2008b,c; Flotho and Melchior, 2013; Krumova and Weishaupt, 2013). Transient brain ischemia is a severe form of metabolic stress that triggers dramatic activation of SUMO2/3 conjugation, and to a lesser extent, SUMO1 conjugation (Yang et al., 2014). It has been proposed that this is a protective response that shields neurons from damage induced by ischemia (Yang et al., 2008a, 2016; Lee and Hallenbeck, 2013). Indeed, results from in vitro and in vivo studies support this notion. For example, neurons in which SUMO2/3 expression is silenced by lentiviral delivery of SUMO2 and SUMO3 microRNAs (miRNAs), are highly sensitive to transient oxygen/glucose deprivation (OGD, an experimental model that simulates ischemia in cells), whereas transgenic mice overexpressing SUMO conjugating enzyme Ubc9, have higher levels of SUMO1- and SUMO2/3-conjugated proteins and smaller infarcts after stroke (Datwyler et al., 2011; Lee et al., 2011). However, we still do not know the role of SUMO conjugation in post-ischemic neurologic function, which ultimately defines quality of life for patients suffering from ischemic brain damage, and how SUMOylation modulates the genome regulated by transient ischemia. Here, we report our findings from the first experimental study that clarifies the contribution of SUMO conjugation to pre- and post-ischemic gene expression and functional outcome. For this study, we used a recently developed neuron-specific SUMO1-3 knockdown (SUMO-KD) mouse model (Wang et al., 2014a).

EXPERIMENTAL PROCEDURES

Animals

All animal experiments were approved by the Duke University Animal Care and Use Committee. A total of 72 mice were used in this study. SUMO-KD transgenic mice were previously generated in our laboratory (Wang et al., 2014a). In this transgenic mouse model, the transgene contains 3 distinct miRNAs that target SUMO1, 2, and 3, and are expressed under the control of the neuron-specific Thy1 promoter. Green fluorescent protein (GFP) is co-expressed as indicator of transgene expression. SUMOKD mice have been backcrossed with C57Bl/6 mice for more than 10 generations. Male SUMO-KD and wild-type littermates (2–3 months old) were used in this study.

Transient forebrain ischemia

Transient forebrain ischemia was performed as described previously (Yang et al., 2008c). Briefly, anesthesia was induced with 5% isoflurane and maintained with 1.5–1.8% isoflurane during surgery. The rectal temperature was maintained at 37.0 °C ± 0.2 °C by surface heating or cooling. PE-10 tubes were inserted into the right femoral artery and the right internal jugular vein to continuously monitor arterial blood pressure and to withdraw blood, respectively. Forebrain ischemia was induced by a combination of 10-min bilateral common carotid artery occlusion, and blood withdrawal-induced hypotension (mean arterial blood pressure = 30 mmHg). To end the ischemic episode, the carotid arteries were de-occluded and withdrawn blood was re-infused. Sham-operated mice underwent the same procedures except carotid artery occlusion and blood withdrawal. To determine whether SUMO knockdown had any effect on blood flow reduction in our transient forebrain ischemia model, a cohort of mice was subjected to blood flow measurements. Before inducing ischemia, a microprobe (Moor) was affixed to the surface of the right parietal skull to monitor regional cerebral blood flow (rCBF) in the middle cerebral artery territory by Laser Doppler flowmetry (Moor).

Tissue sample preparation

At the indicated times of reperfusion, mice were sacrificed, and brains were quickly removed. CA1 and cortex samples were excised in a cryostat set at −20 °C. Tissue samples were stored at −80 °C and later used for RNA or protein preparation. For immunohistochemistry analysis, transcardial perfusion was performed using 4% paraformaldehyde. Brains were collected and fixed overnight. The fixed brains were either embedded in paraffin or immersed in 20% sucrose at 4 °C before stored in −80 °C.

Microarray analysis

CA1 subfield tissue samples were harvested from 4 experimental groups: wild-type sham (WS), wild-type ischemia (WI), SUMO-KD sham (TS), and SUMO-KD ischemia (TI). Post-ischemia samples were collected at 3 h reperfusion. For each group, samples were prepared in triplicate. To minimize variation in biological replicates, CA1 subfield samples from two mouse brains were pooled, and used to prepare total RNA for one independent microarray sample. The Affymetrix GeneChip Mouse Genome 430A 2.0 Array, which contains approximately 14,000 well characterized mouse genes, was used. Synthesis of cDNA, labeling of samples, and array processing was performed at the Duke Sequencing and Genomic Technologies facility (Yang et al., 2009). Partek Genomics Suite 6.6 (Partek) was used to identify differentially expressed genes, and to perform principal component analysis (PCA). Robust multi-chip analysis (RMA) normalization was performed on the entire data set. The differentially expressed genes were selected based on a p value <0.05 (as determined by ANOVA), and a fold-change ≥2. The differentially expressed genes were further analyzed using PANTHER (http://www.pantherdb.org/) and DAVID (https://david.ncifcrf.gov/) to identify enriched genes according to gene ontology (GO) classifications and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.

Quantitative PCR

Quantitative real-time PCR (qPCR) was performed as previously described (Yang et al., 2009). In short, total RNA was prepared from CA1 tissue samples using the TRIzol reagent (Invitrogen). Total RNA (200 ng) was reverse transcribed into cDNA (Invitrogen). qPCR was performed in a Lightcycler 2.0 (Roche). Fold changes were calculated according to the comparative threshold cycle (Ct) method (Schmittgen and Livak, 2008). All primers used in this study are listed in Table 1.

Table 1.

List of primers

Gene Primer sequences (5′->3′)
Sumo1 Forward: CAGGAGGCAAAACCTTCAAC
Reverse: CTCCATTCCCAGTTCTTTCG
Sumo2 Forward: ACGAGAAACCCAAGGAAGGA
Reverse: CTCCATTTCCAACTGTGCAG
Sumo3 Forward: AGAAGCCCAAGGAGGGTGT
Reverse: CCTCGGGAGGCTGATCCT
Atf3 Forward: CCAGGTCTCTGCCTCAGAAG
Reverse: CCTTCAGCTCAGCATTCACA
Hspb1 Forward: GCCTCTTCGATCAAGCTTTC
Reverse: CCTCAGGGGATAGGGAAGAG
Fos Forward: ATGGGCTCTCCTGTCAACAC
Reverse: GCAGCCATCTTATTCCGTTC
Arc Forward: AGCAGCAGACCTGACATCCT
Reverse: GTGATGCCCTTTCCAGACAT
Rgs2 Forward: GAGGAGAAGCGGGAGAAAAT
Reverse: GAGGACAGTTTTTGGGGTGA
Tcfl5 Forward: GGAGGACCGCTTCAACAGTA
Reverse: GGCAGTCCAATATCCTGGTG
Cxcl12 Forward: GCGCTCTGCATCAGTGAC
Reverse: TAATTTCGGGTCAATGCACA
Socs2 Forward: CGCGAGCTCAGTCAAACAG
Reverse: GCAGAGTGGGTGCTGATGTA
Ogt Forward: GCGTTTTCCAGCAGTAGGAG
Reverse: CCAGACTTTGCCACGAATTT
Slco1a4 Forward: AATGCCAAAGAGGAGAAGCA
Reverse: TGGGAAATTGTCACAGGTCA
Rasl10a Forward: TCATCCGCCAATTCTTGTTT
Reverse: TTGTTGCCTACCACCAGGAT
β-actin Forward: TAGGCACCAGGGTGTGATG
Reverse: GGGGTGTTGAAGGTCTCAAA

Western blot analysis

Western blotting was conducted as described before (Yang et al., 2014). Briefly, protein samples were run on SDS–PAGE pre-cast gels (Bio-Rad), and were transferred to PVDF membranes. Membranes were blocked with TBST containing 5% milk, and incubated with a primary antibody overnight at 4 °C. After extensive washing, membranes were incubated with a secondary antibody for 1 h at room temperature. Proteins were then visualized using the enhanced chemiluminescence analysis system (GE Healthcare). After exposure, membranes were stripped and re-probed for β-actin as loading control. Image analysis was performed using the ImageJ program (NIH). The following primary antibodies were used: mouse monoclonal anti-SUMO1 (21C7; DSHB Hybridoma), rabbit polyclonal anti-SUMO2/3 (Covance), rabbit polyclonal anti-GFP (Invitrogen), and mouse monoclonal anti- β -actin (Sigma).

Immunofluorescence

Immunofluorescence staining was performed on paraffin-embedded brain sections (for SUMO1) or frozen brain sections (for SUMO2/3), as described previously (Yang et al., 2014). In short, after deparaffinization, brain sections (5-μm-thick) were incubated with primary antibodies at 4 °C overnight, followed by appropriate secondary fluorescent antibodies for 1 h at room temperature. The frozen brain sections (25 μm) were immunostained using a free-floating staining method. Confocal images were captured on a Leica SP5 confocal microscope (Leica Microsystems). The following primary antibodies were used: mouse monoclonal anti-SUMO1 (21C7; DSHB Hybridoma), rabbit polyclonal anti-SUMO2/3 (Covance), mouse monoclonal anti-GFP (Millipore), and rabbit polyclonal anti-GFP (Invitrogen).

Neurologic score system

Neurologic deficits were assessed by an observer blinded to the genotype of animals using a 9-point score system (Wellons et al., 2000). The assessment was performed before (Pre) and on day 4 after (Post) forebrain ischemia. After testing was complete, the score for each animal was the sum of the individual scores, with 0 = normal and 9 = severe injury.

Statistical analysis

The Prism 6 software (GraphPad) was used to analyze all data. Statistical analysis was assessed by Mann–Whitney U test on all data except the rCBF data. The rCBF data were analyzed by a 2-way analysis of variance (ANOVA) with Bonferroni's post hoc test for multiple comparisons. P values ≤0.05 were considered significant.

RESULTS

Effect of ischemia on SUMOylation in SUMO knockdown mice

Detailed characterization of SUMO-KD mice has been described (Wang et al., 2014a). In this mouse model, three miRNAs that target SUMO1-3 are expressed together with GFP as indicator of transgene expression. Expression of designed miRNAs is driven by the Thy-1 promoter to achieve neuron-specific silencing of SUMO1-3. For the current study, we used SUMO-KD line 27 mice in which GFP is widely expressed in layer V of the cerebral cortex, and the hippocampal CA1 subfield (Wang et al., 2014a). Our earlier quantitative analysis revealed that in the hippocampal CA1 subfield, GFP is expressed in about 70% of neurons. To evaluate the change in SUMOylation after ischemia in SUMO-KD mice, we subjected wild-type and SUMO-KD mice to 10-min forebrain ischemia and 1 h reperfusion. Consistent with our previous findings (Yang et al., 2008c, 2014), levels of SUMO2/3-conjugated proteins in wild-type mice increased massively in both the cortex and hippocampus after brain ischemia (Fig. 1A, B). In SUMO-KD mice, however, the increase in post-ischemic SUMOylation was notably less (Fig. 1A, B). Quantitative Western blotting analysis indicated that the induction fold of SUMO2/3 conjugation in SUMO-KD was around 50% of that found in wild-type mice (Fig. 1C, D; Mann–Whitney U test, p ≤ 0.05, n = 3/group).

Fig. 1.

Fig. 1

SUMOylation after transient forebrain ischemia in SUMO knockdown (SUMO-KD) mice. Wild-type (WT) and SUMO-KD mice were subjected to sham surgery or 10 10-min forebrain ischemia and 1 h reperfusion. Ischemia-induced changes in SUMOylation, and its subcellular localization were evaluated by Western blotting (A–D) and immunohistochemistry (E, F). (A–D) Global SUMOylation in cortex (A, C) and hippocampus (B, D). Global SUMOylation induced by ischemia/reperfusion was significantly less in SUMO-KD mice. The high-molecular-weight regions, marked by brackets, were used for quantification of SUMO2/3 conjugation. Intensities of SUMO2/3 conjugates were measured by image analysis, and normalized to β-actin. Horizontal bar = median values; *p ≤ 0.05. (E, F) Immunohistochemistry analysis of SUMO2/3 (E) and SUMO1 (F) in brains of SUMO-KD mice subjected to sham or ischemia surgery. After ischemia, strong nuclear SUMO2/3 staining was observed in GFP-negative hippocampus neurons (arrows), but was absent in SUMO knockdown neurons (GFP GFP-positive; arrowheads). Nuclear rim staining by SUMO1 appeared more intense in GFP GFP-negative neurons (arrows) compared to GFP GFP-positive cells (arrowheads). Scale bar = 20 μm.

We also used immunohistochemistry to evaluate the efficacy of SUMO1-3 miRNAs to silence SUMO expression (Fig. 1E, F). Double fluorescence immunostaining with anti-GFP and anti-SUMO2/3 antibodies revealed that the robust nuclear accumulation of SUMO2/3-conjugated proteins in post-ischemic GFP-negative neurons (Fig. 1E, arrows) was absent in GFP-positive cells (Fig. 1E, arrowheads). As expected, nuclear rim staining was observed for SUMO1. Unlike SUMO2/3, there was no dramatic increase in SUMO1-conjugated proteins nor obvious change in subcellular localization of SUMO1 after ischemia. However, the signal intensity of SUMO1 staining appeared less in GFP-positive neurons (Fig. 1F, arrowheads) than in GFP-negative neurons (Fig. 1F, arrows). Together, our data confirmed that the post-ischemic increase in SUMOylation was effectively suppressed in SUMO-KD mice.

Effects of ischemia on gene expression in SUMO knockdown mice

Our knowledge of the modulating effects of SUMO conjugation on gene expression is mostly based on results from in vitro cell culture studies. For this first genome-wide analysis of genes differentially regulated after brain ischemia in wild-type and SUMO-KD mice, we focused on the hippocampal CA1 subfield because CA1 neurons are particularly sensitive to transient ischemia, and SUMO expression is effectively silenced in most CA1 neurons of SUMO-KD mice (Fig. 1). Further, CA1 neurons play a key role in memory processes, and SUMO-KD mice are impaired in episodic and fear memory (Wang et al., 2014a). Since we have shown that the peak level of SUMO conjugated proteins in the brain induced by global forebrain ischemia is at 1 h of reperfusion (Yang et al., 2014), we decided to use brain samples collected at 3 h of reperfusion after ischemia for microarray analysis.

Microarray analysis was performed on samples prepared in triplicate from four groups: WS and WI, and SUMO-KD transgenic sham (TS) and ischemia (TI). The hippocampal CA1 subfield tissues were carefully excised, as indicated in Fig. 2A, and used for RNA preparation and microarray analysis. The raw data from the current study have been deposited in NCBI's Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/), and are accessible through GEO Series accession number GSE80681. An overview of microarray results is depicted in Fig. 2. First, we performed data analysis on the global gene expression profiles of all 12 samples by plotting individual samples in a 3-dimensional space based on principal components analysis (PCA; Fig. 2B). PCA demonstrated a clear separation between sham and ischemia, and between wild-type and SUMO-KD, indicating excellent reproducibility of samples and apparent effects of SUMO knockdown and ischemia on gene expression.

Fig. 2.

Fig. 2

Overview of microarray data. Data analysis was performed on the global gene expression profiles of 12 samples from four groups: wild-type (WT) sham (WS), and ischemia (WI); and SUMO-KD (TG) sham (TS), and ischemia (TI). (A) The sampling regions. The region of hippocampal CA1 subfield that was dissected out and used for microarray analysis and qPCR is marked with white dot lines in a representative brain slice of SUMO-KD mice with GFP fluorescence. (B) Principal component analysis (PCA). The individual samples were plotted in a 3-dimensional space based on three principal components. Four groups of samples are clustered according to the genotype and surgery. (C) Venn diagram. The numbers of differentially regulated genes that were identified by pairwise comparisons of groups, with a cut-off of ≥ 2-twofold increase (↑) or decrease (↓) in gene expression are shown. (D) Verification of SUMO1-3 knockdown in SUMO-KD mice. The RNA samples from the sham group that were used for the microarray study, were analyzed to determine the levels of SUMO1-3 mRNA levels in WT and SUMO-KD mice. All individual data were normalized to β-actin. To calculate fold change, the mean values of WT mouse samples were set to 1.0. Horizontal bar = median values; *p ≤ 0.05.

We then defined selection criteria (≥ twofold change and p < 0.05) to identify genes differentially regulated in wild-type and SUMO-KD mice subjected to sham or ischemia surgery. The genes identified from different comparisons are listed in the Appendix Table and overviewed in Fig. 2C. To validate microarray data, we selected 11 of these genes, and performed qPCR analysis (Table 2). The same trend of expression change in the respective comparison, ie, up-regulation or down-regulation, was observed for all selected genes, although the fold changes of some genes were greater in the qPCR analysis than in the microarray data. Thus, the qPCR results validated our microarray data.

Table 2.

Verification of microarray data by qPCR analysis

Entrez gene Gene symbol WI vs WS
TI vs TS
TS vs WS
qPCR Microarray qPCR Microarray qPCR Microarray
11910 Atf3 123.93 46.7 103.25 33.1 −1.46 −1.2
15507 Hspb1 42.71 10.7 3.83 15.2 2.28 −1.2
14281 Fos 39.58 11.4 64.74 20.2 −1.79 −1.8
11838 Arc 11.00 6.15 12.38 8.25 −2.73 −2.45
19735 Rgs2 3.86 4.1 1.43 1.9 −1.08 −1.1
277353 Tcfl5 3.36 1.56 0.83 −1.27 261.38 38.58
20315 Cxcl12 −1.82 −1.4 −1.96 −1.32 −1.91 −2.45
216233 Socs2 −1.36 1.95 1.17 2.18 −2.40 −1.1
108155 Ogt −2.21 −2.3 −1.89 −2.2 −0.96 1.2
28250 Slco1a4 −5.15 −2.6 −2.13 −2.3 −1.04 −1.1
75668 Rasl10a −6.39 −2.9 −3.26 −2.0 −1.13 −1.1

To characterize the effects of genotype and ischemia on gene regulation, we performed pairwise comparison of groups (Appendix Table). The number of differentially regulated genes among all 3 comparisons, and their expression changes after ischemia (up- or down-regulated) are presented in the Venn diagram in Fig. 2C A large number of genes were differentially regulated by ischemia in both wild-type and SUMO-KD mice. In wild-type mice, 419 genes were regulated by ischemia (Fig. 2C; WI vs WS), while 270 genes were regulated by ischemia in SUMO-KD mice (Fig. 2C; TI vs TS). However, a total of 196 genes showed ischemia-induced differential expression uniquely in wild-type mice, more than that in SUMO-KD mice. In sham animals, 64 genes were differently regulated by silencing SUMO expression, and most of these genes were up-regulated (Fig. 2C; TS vs WS). Notably, only one gene showed up in all three pairwise comparisons – the gene coding for the activity-regulated cytoskeleton-associated protein (Arc; also known as Arg3.1). Specifically, Arc was significantly down-regulated in SUMO-KD sham mice. After ischemia, it was up-regulated in both wild-type and SUMO-KD mice.

Microarray data show that the expression levels of SUMO1-3 decreased but with a fold change <2 in SUMO-KD mice compared to wild-type mice, and therefore, according to our pre-defined criteria, none of the three SUMOs were identified as differentially regulated genes (Appendix Table). To verify that expression of all SUMOs was indeed silenced in SUMO-KD mice, we performed qPCR on the hippocampal CA1 samples. The qPCR analysis revealed that SUMO1-3 mRNA levels in SUMO-KD mice were significantly reduced to 51.6% ± 6.7% (SUMO1), 44.3% ± 4.9% (SUMO2), and 53.1% ± 8.4% (SUMO3) compared to wild-type (Fig. 2D; mean ± SEM, Mann–Whitney U test, p ≤ 0.05, n = 3/group). This confirms the high capacity of SUMO miRNAs to silence SUMO expression, considering that SUMOs are expressed in all mammalian cells, and that here, SUMO is knocked down only in neurons of which about 70% express SUMO miRNAs in the hippocampal CA1 subfield. Taken together, the microarray analysis generated a reliable dataset of genes that are differentially regulated by SUMO conjugation in the CA1 subfield after brain ischemia.

Effects of ischemia on processes and pathways in SUMO knockdown mice

We then analyzed our microarray data based on two widely used databases – GO categories and KEGG pathways. GO and KEGG pathway analyses of differentially expressed genes in the CA1 subfield after forebrain ischemia in wild-type and SUMO-KD mice are depicted in Figs. 3 and 4, respectively. Overall, enriched GO terms according to protein class and biological processes, overlapped almost completely between wild-type and SUMO-KD mice. The list of enriched KEGG pathways show some overlaps but also some distinct differences between genotypes. In both datasets, the mitogen-activated protein kinase (MAPK) signaling pathway is particularly enriched, followed by Jak-STAT, p53, and ErbB signaling pathways (Figs. 3 and 4C and C). In these lists, ECM-receptor interaction, endocytosis, and focal adhesion pathways showed up only in SUMO-KD mice after ischemia (Fig. 4C), whereas other pathways, such as TGF-beta, Toll-like receptor, and Wnt signaling, were identified only in wild-type mice after ischemia (Fig. 3C).

Fig. 3.

Fig. 3

GO classification and KEGG pathway analysis of differentially expressed genes in the CA1 samples after forebrain ischemia in wild-type mice. (A) Enriched GO terms according to protein class. (B) Enriched GO terms according to biological processes. (C) Enriched KEGG pathways.

Fig. 4.

Fig. 4

GO classification and KEGG pathway analysis of differentially expressed genes in the CA1 samples after forebrain ischemia in SUMO-KD mice. (A) Enriched GO terms according to protein class. (B) Enriched GO terms according to biological processes. (C) Enriched KEGG pathways.

Gene expression in neurons before and after ischemia in SUMO knockdown mice

Our microarray results suggest that when SUMO expression is silenced in neurons, gene expression is differentially modulated in physiologic vs post-ischemic states (Fig. 2). Fig. 5 shows a visual representation of all genes that were differentially expressed in wild-type and SUMO-KD mice before (Fig. 5A) and after ischemia (Fig. 5B). Notably, of the 64 genes that were regulated by SUMOylation in the physiologic state, 60 were up-regulated, and only four were down-regulated in SUMO-KD mice (Fig. 5A). This observation supports a model whereby in non-stressed neurons SUMO conjugation negatively regulates gene expression in vivo. To better visualize the effect of SUMO conjugation on gene expression after ischemia, we compared the fold change of all 223 genes regulated by ischemia in both wild-type and SUMO-KD mice (Fig. 5B). Notably, about 70% of these genes showed a greater fold-change in wild-type compared to SUMO-KD mice (Fig. 5B, fold change ratio below 1), indicating that knockdown of SUMO expression suppresses the post-ischemic activation of gene expression.

Fig. 5.

Fig. 5

Effect of SUMO knockdown on differentially expressed genes in the CA1 subfield before and after ischemia. (A) Fold change of genes differentially regulated in the SUMO-KD sham group (TS) compared to the wild-type sham group (WS). (B) The ratio of fold change of the genes differentially regulated by ischemia in both SUMO-KD (TG) and wild-type (WT) mice. The ratio was calculated by dividing an ischemia-induced fold change of a gene between TG and WT mice. If the ratio of a gene is < 1, the fold change of this gene regulated by ischemia is greater in WT mice.

Functional recovery after transient forebrain ischemia in SUMO knockdown mice

Results from a variety of in vitro and in vivo studies suggest that the post-ischemic activation of SUMO conjugation is a neuroprotective stress response. Recovery of neurologic function defines quality of life for patients who have suffered an ischemic attack; however, the effect of SUMO conjugation on functional recovery after ischemia has not yet been studied. To address this important aspect, we first confirmed that neuron-specific SUMO knockdown did not affect blood flow reduction in our transient forebrain ischemia model (Fig. 6A). Then, we used a 9-point scoring system to evaluate neurologic function before and 4 days after 10-min forebrain ischemia in wild-type and SUMO-KD mice. We did not find a significant difference in neurologic scores between wild-type and SUMO-KD mice before ischemia (Fig. 6B). After ischemia, however, impairment of neurologic functions was significantly more pronounced in SUMO-KD compared to wild-type mice (Fig. 6B; Mann–Whitney U test, p ≤ 0.01; n = 10 or 11/group).

Fig. 6.

Fig. 6

Functional outcome after transient forebrain ischemia. (A) Effect of SUMO knockdown on rCBF in our transient forebrain ischemia model. Wild-type (WT; n = 5) and SUMO-KD (n = 5) mice were subjected to 10 10-min forebrain ischemia. Data are presented as means ± SEM. Laser-Doppler measurements revealed a similar change in rCBF between WT and SUMO-KD mice during ischemia and reperfusion. (B) Wild-type (WT; n = 10) and SUMO-KD (n = 11) mice were subjected to 10 10-min forebrain ischemia. Neurologic function was evaluated 1 day before (Pre) and 4 days after (Post) forebrain ischemia. Horizontal bar = median values. ns, not significant; **p ≤ 0.01.

DISCUSSION

Recently, SUMO conjugation has attracted attention in neuroscience, because this post-translational protein modification plays key roles in physiologic neurologic functions, including memory processes, and is associated with a variety of diseases of major clinical significance including brain tumor, brain ischemia, and neurodegenerative diseases (Yang et al., 2008b,c, 2013; Flotho and Melchior, 2013; Krumova and Weishaupt, 2013). Therefore, it is important to understand how SUMOylation impacts the physiologic/disease process under investigation. We know that many SUMO targets are nuclear proteins involved in gene expression, but there is little information about how SUMOylation modulates gene expression in vivo because prior studies have been conducted predominantly in vitro. The tools are now available to modulate SUMO in vivo only in cells that are targets of the physiologic/pathologic process under investigation. Recently, we developed a mouse model (SUMO-KD) in which expression of all three SUMO iso-forms is silenced specifically in neurons. This new mouse model has allowed us, for the first time, to study the effect of SUMO conjugation on gene expression in neurons in vivo, both in the physiologic state and in the diseases associated with SUMO conjugation, and to elucidate the role of SUMOylation in functional recovery of neurons exposed to ischemic stress.

Neurons are extremely sensitive to stress conditions; neurologic function is impaired in many diseases including brain ischemia/stroke, neurodegenerative diseases, and neuropsychiatric conditions. Further, post-ischemic recovery of neuronal function and the capacity of the brain to activate SUMO conjugation when challenged by ischemic stress decline with advanced age (Liu et al., 2016). Therefore, our new mouse model and the results presented here could be of broad interest. It is important to note that the gene expression profiles reported here were evaluated by microarray analysis on the hippocampal CA1 samples. Thus, these findings represent changes that occurred in all cell types present in the sample. However, the effects of SUMOylation on gene expression relate predominantly to neurons because we used a neuron-specific promoter to express SUMO1-3 miRNAs to silence SUMO expression.

For this in vivo study on the effects of SUMO conjugation on gene expression, we used brain ischemia as the pathologic state of interest because we have already shown that brain ischemia massively activates SUMO conjugation and nuclear accumulation of SUMO2/3-conjugated proteins (Yang et al., 2008b,c, 2014). Further, it is widely appreciated that the post-ischemic activation of SUMO conjugation is a protective stress response that shields neurons from injury, as evidenced in in vitro and in vivo studies (Lee et al., 2007, 2009, 2011, 2016; Datwyler et al., 2011). However, the effect of SUMO conjugation on post-ischemic neurologic function has not yet been investigated. The most important findings in the present study can be summarized as follows: (a) in the physiologic state of neurons, expression of most genes regulated by SUMOylation was activated by silencing SUMO expression; (b) in most cases, the effects of ischemia on gene expression were less pronounced in SUMO-KD than in wild-type mice; and (c) silencing SUMO expression worsened neurologic function after brain ischemia. These findings will be discussed in detail below.

Here, we reported a genomic study on hippocampal CA1 subfield tissue samples from mice, to identify genes regulated by ischemia. To date, only a few studies have applied the microarray technology to analyze gene expression modulated by global brain ischemia in samples excised from the CA1 subfield, whole hippocampus, or whole hemisphere (Jin et al., 2001; Kawahara et al., 2004; Yakubov et al., 2004; Feng et al., 2007; Buttner et al., 2009). For a comprehensive discussion see also Schmidt-Kastner, 2015 (Schmidt-Kastner, 2015). All of these studies used rat models, and only 2 studies used microarrays representing more than 10,000 genes (Feng et al., 2007; Buttner et al., 2009). Since these two studies used a post-ischemic time point for analysis similar to our study, we compared our list of genes regulated by ischemia with the lists from these studies. We found a large overlap of genes identified, including Atf3, Jun, Fos, Ptgs2, Gadd45, Hmox1, Hsp70, Hsp27, and also overlap of the highly enriched pathways, based on KEGG analysis, including MAPK, Wnt, TGF- β, and Toll-like receptor pathways. These comparisons support the validity of our dataset.

One of the key findings of our study reported here was that silencing SUMO expression in hippocampal CA1 neurons in vivo had opposite effects on global gene expression in the physiologic state vs the post-ischemia state. Silencing SUMO expression up-regulated gene expression in non-stressed neurons, but suppressed global gene expression responses induced by transient ischemia. At first glance, the observation that the global gene expression response induced by transient ischemia was suppressed in SUMO-KD mice was an unexpected finding, because until recently, it was generally believed that SUMOylation of most transcription factors negatively regulates their activity. Indeed, studies on a number of individual SUMO targets involved in transcription show that SUMOylation reduces the transcription activity of most of these targets (Chymkowitch et al., 2015). However, comprehensive characterization of transcriptional regulation by SUMOylation on chromatin using ChIP-seq techniques, revealed a more complex role for SUMOylation in gene expression.

Using human fibroblasts for ChIP-seq analysis, SUMOylated proteins were found at promoters of many genes involved in cell growth and proliferation, and inhibition of SUMOylation up-regulated transcription of those genes (Neyret-Kahn et al., 2013). Another study, however, reported that SUMOylation has a positive effect on transcription of genes in stressed cell (Seifert et al., 2015). Notably, using ChIP-seq and RNA-seq techniques, and heat shock as the stress condition, the authors found markedly increased binding of SUMO2-conjugated proteins to active DNA regulatory regions of many pro-survival genes. This observation supports the notion that stress-induced activation of SUMO2/3 conjugation is a protective stress response that shields stressed cells from damage by activating expression of pro-survival genes. Therefore, blocking this pro-survival response in SUMOKD mice may have contributed to the worse functional outcome after transient forebrain ischemia. Together, although our study reported here focused on terminally differentiated neurons in vivo, whereas earlier studies performed analyses on dividing cells in vitro, the modulating effects of SUMOylation on gene expression were similar, ie, suppressing gene expression in the physiologic state and activating expression of groups of genes when cells are stressed.

Considering the observation that in heat shock-stressed cells, SUMO2 conjugation activates expression of pro-survival genes, we analyzed our dataset to identify pro-survival genes with suppressed ischemia-induced activation in SUMO-KD mice. DAVID analysis identified eight anti-apoptosis genes of which seven were less activated in SUMO-KD mice after ischemia: Bag3, Cited2, Cflar, Bdnf, Hells, Myc, and Cebp β. For example, Bag3, which was identified as an ischemia-regulated gene in an earlier microarray study (Schmidt-Kastner et al., 2002), codes for a protein with anti-apoptosis function through interaction with Hsp70 (Rosati et al., 2011). Activation of the growth arrest and DNA damage 45 (Gadd45) gene family was also suppressed after ischemia in SUMO-KD mice. All 3 members of this gene family – Gadd45a, Gadd45b, and Gadd45g – have been identified as ischemia-regulated genes and they may play a protective role in brain ischemia injury (Chen et al., 1998; Sultan and Sweatt, 2013).

It is also noteworthy that Arc is one of the few genes that were down-regulated in SUMO-KD mice in the physiologic state. This could be a finding of significant interest, because Arc is critical for embryogenesis, and is a pivotal regulator of synaptic plasticity (Liu et al., 2000; Shepherd and Bear, 2011). Both processes are modulated by SUMOylation. The potential consequences of SUMO-modulated Arc expression in embryogenesis and synaptic plasticity should, therefore, be elucidated in future studies.

In conclusion, we used SUMO knockdown transgenic mice to perform the first in vivo analysis of global SUMOylation on the transcriptome in neurons regulated by transient forebrain ischemia. Notably, earlier studies that analyzed the effect of SUMOylation on the transcriptome were performed in vitro and exposed cells to a single stress such as heat shock. Further, we provide the first evidence that silencing SUMO expression worsened functional outcome after brain ischemia. Thus, the present findings, together with earlier reports on the role of SUMOylation in brain ischemia, support that SUMOylation is a neuroprotective response, at least in part, through transcriptional regulation of stress response genes.

Acknowledgments

We thank Pei Miao for her excellent technical support, and Kathy Gage for her excellent editorial contributions. This study was supported by American Heart Association grant 12SDG11950003 (to W.Y.), and by National Institutes of Health R01 grants NS081299 and NS097554 (to W.P.). X.L. is supported by the grant from the National Natural Science Foundation of China (#81471175).

Abbreviations

ANOVA

analysis of variance

Arc

activity-regulated cytoskeleton-associated protein

GFP

green fluorescent protein

GO

gene ontology

KEGG

Kyoto Encyclopedia of Genes and Genomes

MAPK

mitogen-activated protein kinase

miRNA

microRNA

OGD

oxygen/glucose deprivation

PCA

principal component analysis

qPCR

quantitative real-time PCR

RanGAP1

Ran GTPase-activating protein-1

rCBF

regional cerebral blood flow

SUMO

small ubiquitin-like modifier

SUMO-KD

SUMO1-3 knockdown

WI

wild-type ischemia

WS

wild-type sham

APPENDIX A

WI vs WS (194 genes)
Probeset ID Entrez Gene Gene Symbol Gene Title RefSeq Transcript ID WI vs WS TI vs TS TS vs WS
1449827_at 11595 Acan aggrecan NM_007424 7.3 2.2 −1.1
1422053_at 16323 Inhba inhibin beta-A NM_008380 5.4 1.2 −1.4
1421009_at 58185 Rsad2 radical S-adenosyl methionine domain containing 2 NM_021384 5.3 2.6 −1.0
1419220_at 22437 Xirp1 xin actin-binding repeat containing 1 NM_001081339 /// NM_011724 5.2 1.1 −1.1
1437279_x_at 20969 Sdc1 syndecan 1 NM_011519 5.2 2.0 1.3
1418930_at 15945 Cxcl10 chemokine (C-X-C motif) ligand 10 NM_021274 5.1 2.3 −1.1
1419247_at 19735 Rgs2 regulator of G-protein signaling 2 NM_009061 4.1 1.9 −1.1
1423310_at 21983 Tpbg trophoblast glycoprotein NM_001164792 /// NM_011627 3.8 1.8 1.9
1424229_at 226419 Dyrk3 dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 3 NM_145508 3.8 1.5 1.1
1418392_a_at 55932 Gbp3 guanylate binding protein 3 NM_018734 3.8 1.7 1.2
1435137_s_at 319269 1200015M12Rik /// A130040M12Rik RIKEN cDNA 1200015M12 gene /// RIKEN cDNA A130040M12 gene NR_002860 3.7 2.8 −1.2
1416579_a_at 17075 Epcam epithelial cell adhesion molecule NM_008532 3.6 1.8 −1.0
1418203_at 58801 Pmaip1 phorbol-12-myristate-13-acetate-induced protein 1 NM_021451 3.6 1.8 1.7
1421134_at 11839 Areg amphiregulin NM_009704 3.5 1.4 −1.0
1428781_at 73712 Dmkn dermokine NM_001166173 /// NM_001166174 /// NM_028618 /// NM_172899 3.5 1.3 −1.2
1455271_at 620695 Gm13889 predicted gene 13889 NM_001145034 3.3 2.0 1.4
1418240_at 14469 Gbp2 guanylate binding protein 2 NM_010260 3.3 1.7 −1.2
1417487_at 14283 Fosl1 fos-like antigen 1 NM_010235 3.2 1.9 1.1
1424711_at 83921 Tmem2 transmembrane protein 2 NM_001033759 /// NM_031997 3.2 1.6 1.2
1450698_at 13537 Dusp2 dual specificity phosphatase 2 NM_010090 3.2 1.7 1.0
1418538_at 105785 Kdelr3 KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 3 NM_134090 3.1 1.7 −1.1
1420591_at 80910 Gpr84 G protein-coupled receptor 84 NM_030720 3.1 2.0 −1.1
1419766_at 17691 Sik1 salt inducible kinase 1 NM_010831 3.1 1.9 1.2
1453238_s_at 319269 A130040M12Rik RIKEN cDNA A130040M12 gene NR_002860 3.0 2.5 −1.2
1449824_at 96875 Prg4 proteoglycan 4 (megakaryocyte stimulating factor, articular superficial zone protein) NM_001110146 /// NM_021400 3.0 2.1 −1.5
1449484_at 20856 Stc2 stanniocalcin 2 NM_011491 2.9 2.3 −1.3
1423233_at 12609 Cebpd CCAAT/enhancer binding protein (C/EBP), delta NM_007679 2.9 2.0 1.4
1424130_a_at 19285 Ptrf polymerase I and transcript release factor NM_008986 2.9 1.4 −1.2
1427359_at 338523 Jhdm1d jumonji C domain-containing histone demethylase 1 homolog D (S. cerevisiae) NM_001033430 2.8 1.7 −1.1
1449025_at 15959 Ifit3 interferon-induced protein with tetratricopeptide repeats 3 NM_010501 2.8 1.5 1.2
1449031_at 12705 Cited1 Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 1 NM_001276466 /// NM_001276473 /// NM_001276474 /// NM_007709 2.8 1.8 1.3
1450783_at 15957 Ifit1 interferon-induced protein with tetratricopeptide repeats 1 NM_008331 2.8 2.1 −1.2
1417051_at 18530 Pcdh8 protocadherin 8 NM_001042726 /// NM_021543 2.8 1.5 1.0
1424594_at 74480 Samd4 sterile alpha moif domain containing 4 NM_001037221 /// NM_001163433 /// NM_028966 2.7 1.9 −1.1
1424289_at 209212 Osgin2 oxidative stress induced growth inhibitor family member 2 NM_145950 2.7 1.8 1.1
1423703_at 235036 Ppan peter pan homolog (Drosophila) NM_145610 2.7 2.0 1.2
1423389_at 17131 Smad7 SMAD family member 7 NM_001042660 /// NM_008543 2.7 1.8 −1.2
1430978_at 75617 Rps25 ribosomal protein S25 NM_024266 2.6 1.6 1.0
1428374_at 93683 Glce glucuronyl C5-epimerase NM_033320 2.6 1.6 1.3
1418135_at 17355 Aff1 AF4/FMR2 family, member 1 NM_001080798 /// NM_133919 2.6 1.5 1.6
1448961_at 18828 Plscr2 phospholipid scramblase 2 NM_001195084 /// NM_008880 2.6 2.0 1.2
1435655_at 269261 Rpl12 ribosomal protein L12 NM_009076 2.6 1.8 1.2
1440831_at 12013 Bach1 BTB and CNC homology 1 NM_007520 2.6 1.9 1.1
1452869_at 66921 Prpf38b PRP38 pre-mRNA processing factor 38 (yeast) domain containing B NM_025845 2.6 2.0 −1.0
1448480_at 66164 Nip7 nuclear import 7 homolog (S. cerevisiae) NM_001164472 /// NM_025391 /// NR_028367 2.6 1.7 1.2
1418666_at 19288 Ptx3 pentraxin related gene NM_008987 2.6 1.9 −1.2
1424932_at 13649 Egfr epidermal growth factor receptor NM_007912 /// NM_207655 2.6 1.9 1.3
1415996_at 56338 Txnip thioredoxin interacting protein NM_001009935 /// NM_023719 2.6 2.3 1.1
1421336_at 19130 Prox1 prospero-related homeobox 1 NM_008937 2.6 1.2 1.4
1416762_at 20194 S100a10 S100 calcium binding protein A10 (calpactin) NM_009112 2.5 1.9 1.2
1426648_at 17164 Mapkapk2 MAP kinase-activated protein kinase 2 NM_008551 2.5 1.6 1.0
1416123_at 12444 Ccnd2 cyclin D2 NM_009829 2.5 1.8 1.2
1429783_at 56376 Pdlim5 PDZ and LIM domain 5 NM_001190852 /// NM_001190853 /// NM_001190854 /// NM_001190855 /// NM_001190856 ///NM 2.5 1.9 1.4
1426871_at 70611 Fbxo33 F-box protein 33 NM_001033156 2.5 1.9 −1.1
1418492_at 23893 Grem2 gremlin 2 homolog, cysteine knot superfamily (Xenopus laevis) NM_011825 2.5 1.7 1.1
1450986_at 55989 Nop58 NOP58 ribonucleoprotein NM_018868 2.5 2.0 1.1
1425037_at 224014 Fgd4 FYVE, RhoGEF and PH domain containing 4 NM_139232 /// NM_139233 /// NM_139234 2.5 1.7 1.3
1418648_at 112407 Egln3 EGL nine homolog 3 (C. elegans) NM_028133 2.5 1.5 −1.3
1424371_at 228769 Psmf1 proteasome (prosome, macropain) inhibitor subunit 1 NM_144889 /// NM_212446 2.5 1.7 1.4
1451714_a_at 26397 Map2k3 mitogen-activated protein kinase kinase 3 NM_008928 2.5 1.9 1.1
1460335_at 80289 Lysmd3 LysM, putative peptidoglycan-binding, domain containing 3 NM_030257 2.5 1.8 1.1
1424001_at 67949 Mki67ip Mki67 (FHA domain) interacting nucleolar phosphoprotein NM_026472 2.4 1.6 1.0
1420376_a_at 15078 Gm10257 /// Gm12657 /// Gm6749/// H3f3a /// H3f3b /// H3f3c /// LOC101056659 predicted gene 10257 /// predicted gene 12657 /// predicted pseudogene 6749 /// H3 hist NM_001081019 /// NM_008210 /// NM_008211 /// XM_003084942 /// XM_003945939 /// XM_00394 2.4 1.8 1.2
1421375_a_at 20200 S100a6 S100 calcium binding protein A6 (calcyclin) NM_011313 2.4 1.8 1.2
1452192_at 234344 Naf1 nuclear assembly factor 1 homolog (S. cerevisiae) NM_001163564 2.4 1.3 1.1
1434380_at 229900 Gbp7 guanylate binding protein 7 NM_001083312 /// NM_145545 2.4 1.5 1.2
1422706_at 65112 Pmepa1 prostate transmembrane protein, androgen induced 1 NM_022995 2.4 1.7 1.0
1425503_at 14538 Gcnt2 glucosaminyl (N-acetyl) transferase 2, I-branching enzyme NM_008105 /// NM_023887 /// NM_133219 2.4 1.8 1.4
1420380_at 20296 Ccl2 chemokine (C-C motif) ligand 2 NM_011333 2.4 1.8 1.1
1417639_at 30805 Slc22a4 solute carrier family 22 (organic cation transporter), member 4 NM_019687 2.4 1.6 1.3
1419169_at 50772 Mapk6 mitogen-activated protein kinase 6 NM_015806 /// NM_027418 2.4 1.9 −1.1
1424355_a_at 20467 Sin3b transcriptional regulator, SIN3B (yeast) NM_001113248 /// NM_009188 2.4 1.8 1.1
1450718_at 23921 Sh2b2 SH2B adaptor protein 2 NM_018825 2.4 1.9 1.4
1460695_a_at 72061 2010111I01Rik RIKEN cDNA 2010111I01 gene NM_028079 2.4 1.7 1.2
1434128_a_at 232976 Zfp574 zinc finger protein 574 NM_001168506 /// NM_175477 2.3 1.7 1.0
1417508_at 30945 Rnf19a ring finger protein 19A NM_013923 2.3 1.3 1.1
1437843_s_at 71844 Nupl1 nucleoporin like 1 NM_170591 2.3 1.5 1.5
1421365_at 14313 Fst follistatin NM_008046 2.3 1.6 1.1
1449317_at 12633 Cflar CASP8 and FADD-like apoptosis regulator NM_009805 /// NM_207653 2.3 1.7 1.1
1426351_at 15510 Hspd1 /// LOC101056370 heat shock protein 1 (chaperonin) /// 60 kDa heat shock protein, mitochondrial-like NM_010477 /// XM_003946023 2.3 1.9 −1.0
1424107_at 228421 Kif18a kinesin family member 18A NM_139303 2.3 1.5 1.1
1418825_at 15944 Irgm1 immunity-related GTPase family M member 1 NM_008326 2.3 1.1 1.8
1451680_at 76650 Srxn1 sulfiredoxin 1 homolog (S. cerevisiae) NM_029688 2.3 1.4 −1.0
1433502_s_at 104662 Tsr1 TSR1 20S rRNA accumulation NM_177325 2.3 1.7 1.2
1438761_a_at 18263 Odc1 ornithine decarboxylase, structural 1 NM_013614 2.3 1.5 1.2
1431422_a_at 56405 Dusp14 dual specificity phosphatase 14 NM_019819 2.3 1.5 1.3
1425671_at 26556 Homer1 homer homolog 1 (Drosophila) NM_011982 /// NM_147176 /// NM_152134 2.3 1.7 −1.1
1452358_at 24004 Rai2 retinoic acid induced 2 NM_001103367 /// NM_198409 2.3 1.1 1.1
1422473_at 18578 Pde4b phosphodiesterase 4B, cAMP specific NM_001177980 /// NM_001177981 /// NM_001177982 /// NM_001177983 /// NM_019840 2.3 1.7 1.4
1426798_a_at 108954 Ppp1r15b protein phosphatase 1, regulatory (inhibitor) subunit 15b NM_133819 2.3 1.9 1.0
1418834_at 117197 Bloc1s4 biogenesis of organelles complex-1, subunit 4, cappuccino NM_133724 2.3 1.9 1.1
1449007_at 12228 Btg3 /// Gm7334 B cell translocation gene 3 /// B-cell translocation gene 3 pseudogene NM_009770 /// NR_002700 2.3 1.7 1.3
1419765_at 71745 Cul2 cullin 2 NM_029402 2.3 1.8 1.4
1425565_at 19712 Rest RE1-silencing transcription factor NM_011263
1424270_at 13175 Dclk1 doublecortin-like kinase 1 NM_001111051 /// NM_001111052 /// NM_001111053 /// NM_001195538 /// NM_001195539 /// NM 2.2 1.4 1.0
1438992_x_at 11911 Atf4 activating transcription factor 4 NM_009716 2.2 1.9 −1.2
1427321_s_at 13052 Cxadr coxsackie virus and adenovirus receptor NM_001025192 /// NM_001276263 /// NM_009988 2.2 1.7 1.3
1436684_a_at 67045 Riok2 RIO kinase 2 (yeast) NM_025934 2.2 1.5 1.5
1439154_at 269966 Nup98 nucleoporin 98 NM_022979 2.2 1.8 1.1
1435561_at 13875 Erf Ets2 repressor factor NM_010155 2.2 1.7 1.1
1449227_at 12642 Ch25h cholesterol 25-hydroxylase NM_009890 2.2 1.9 1.1
1448133_at 97112 Nmd3 NMD3 homolog (S. cerevisiae) NM_133787 2.2 1.6 1.2
1416106_at 100087 Kti12 KTI12 homolog, chromatin associated (S. cerevisiae) NM_029571 2.2 1.6 1.1
1415806_at 18791 Plat plasminogen activator, tissue NM_008872 2.2 1.8 1.2
1417719_at 60406 Sap30 sin3 associated polypeptide NM_021788 2.2 1.9 1.1
1421267_a_at 17684 Cited2 Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2 NM_010828 2.2 1.4 1.6
1450297_at 16193 Il6 interleukin 6 NM_031168 2.2 1.8 1.0
1434436_at 75746 Morc4 microrchidia 4 NM_001193309 /// NM_029413 2.2 1.8 1.1
1419702_at 21339 Taf1a TATA box binding protein (Tbp)-associated factor, RNA polymerase I, A NM_001277957 /// NM_001277958 /// NM_001277959 /// NM_021466 2.2 1.5 −1.1
1421855_at 14190 Fgl2 fibrinogen-like protein 2 NM_008013 2.2 1.3 1.2
1452997_at 381598 2610005L07Rik cadherin 11 pseudogene NM_001024708 /// NM_001033456 /// NR_028428 2.2 1.5 1.5
1460351_at 20195 Gm12854 /// Gm5068 /// S100a11 predicted gene 12854 /// predicted gene 5068 /// S100 calcium binding protein A11 (calg NM_016740 /// XM_003085822 /// XM_003086388 /// XM_204772 2.2 1.8 −1.1
1448328_at 24055 Sh3bp2 SH3-domain binding protein 2 NM_001136088 /// NM_001145858 /// NM_001145859 /// NM_011893 2.2 2.0 1.3
1420502_at 20229 Sat1 spermidine/spermine N1-acetyl transferase 1 NM_009121 2.2 1.9 −1.0
1459902_at 212772 Arl14ep ADP-ribosylation factor-like 14 effector protein NM_001025102 /// NM_173750 2.2 1.8 1.0
1451533_at 217887 BC022687 cDNA sequence BC022687 NM_145450 2.2 1.5 1.5
1451969_s_at 235587 Parp3 poly (ADP-ribose) polymerase family, member 3 NM_145619 2.2 2.0 −1.1
1418804_at 84112 Sucnr1 succinate receptor 1 NM_032400 2.2 1.2 1.0
1448678_at 73225 Fam118a family with sequence similarity 118, member A NM_133750 /// NM_177067 2.2 1.9 1.1
1423169_at 24074 Taf7 TAF7 RNA polymerase II, TATA box binding protein (TBP)-associated factor NM_175770 2.1 1.6 1.6
1455105_at 19248 Ptpn12 protein tyrosine phosphatase, non-receptor type 12 NM_011203 2.1 1.5 −1.0
1452416_at 16194 Il6ra interleukin 6 receptor, alpha NM_010559 2.1 1.9 1.2
1424211_at 70556 Slc25a33 solute carrier family 25, member 33 NM_027460 /// XM_003945705 2.1 1.4 1.3
1451780_at 17060 Blnk B cell linker NM_008528 2.1 1.6 −1.1
1460428_at 68420 Ankrd13a ankyrin repeat domain 13a NM_026718 2.1 1.8 1.0
1452045_at 226442 Zfp281 zinc finger protein 281 NM_001160251 /// NM_177643 2.1 1.9 −1.0
1436893_a_at 57438 41705 membrane-associated ring finger (C3HC4) 7 NM_020575 2.1 1.6 1.3
1422554_at 66647 Ndnl2 necdin-like 2 NM_023239 2.1 1.8 −1.0
1460657_at 22409 Wnt10a wingless related MMTV integration site 10a NM_009518 2.1 1.3 1.1
1418711_at 18590 Pdgfa platelet derived growth factor, alpha NM_008808 2.1 1.7 −1.0
1454064_a_at 56515 Rnf138 ring finger protein 138 NM_019706 /// NM_207623 2.1 1.5 1.2
1448749_at 56193 Plek pleckstrin NM_019549 2.1 1.9 1.1
1451069_at 223775 Pim3 proviral integration site 3 NM_145478 2.1 1.9 −1.1
1426858_at 16324 Inhbb inhibin beta-B NM_008381 2.1 1.6 1.6
1416359_at 170625 Snx18 sorting nexin 18 NM_130796 2.1 2.0 −1.1
1437111_at 244871 Zc3h12c zinc finger CCCH type containing 12C NM_001162921 2.1 1.8 −1.1
1426609_at 72662 Dis3 DIS3 mitotic control homolog (S. cerevisiae) NM_028315 2.1 1.8 1.1
1450685_at 59046 Arpp19 cAMP-regulated phosphoprotein 19 NM_001142655 /// NM_021548 2.1 1.5 −1.2
1416081_at 17125 Smad1 SMAD family member 1 NM_008539 2.1 1.9 1.1
1425321_a_at 94040 Clmn calmin NM_001040682 /// NM_053155 2.1 1.9 1.1
1418918_at 16006 Igfbp1 insulin-like growth factor binding protein 1 NM_008341 2.1 1.5 1.1
1423904_a_at 52118 Pvr poliovirus receptor NM_027514 2.1 1.5 1.2
1448802_at 27275 Nufip1 nuclear fragile X mental retardation protein interacting protein 1 NM_013745 2.1 1.7 1.1
1434425_at 99681 Tchh trichohyalin NM_001163098 2.1 1.3 1.4
1428114_at 108052 Slc14a1 solute carrier family 14 (urea transporter), member 1 NM_001171010 /// NM_001171011 /// NM_028122 2.1 1.3 1.7
1437696_at 381066 Zfp948 zinc finger protein 948 NM_001002008 2.1 1.4 1.1
1428942_at 17750 Mt2 metallothionein 2 NM_008630 2.1 1.8 1.1
1429040_at 547150 6820431F20Rik cadherin 11 pseudogene NR_030708 2.1 1.3 1.8
1418323_at 14155 Fem1b feminization 1 homolog b (C. elegans) NM_010193 2.1 1.9 1.0
1438511_a_at 66214 Rgcc regulator of cell cycle NM_025427 2.0 1.3 1.1
1449188_at 59090 Midn midnolin NM_021565 2.0 1.7 −1.1
1453100_at 13000 Csnk2a2 casein kinase 2, alpha prime polypeptide NM_009974 2.0 1.7 1.1
1419749_at 13434 Trdmt1 tRNA aspartic acid methyltransferase 1 NM_010067 2.0 1.7 1.3
1436871_at 225027 Srsf7 serine/arginine rich splicing factor 7
-
NM_001195485 /// NM_001195486 /// NM_001195487 /// NM_146083 /// NR_036615 2.0 1.7 1.3
1437396_at 208647 Creb3l2 cAMP responsive element binding protein 3-like 2 NM_178661 2.0 1.7 1.0
1460179_at 15502 Dnaja1 DnaJ (Hsp40) homolog, subfamily A, member 1 NM_001164671 /// NM_001164672 /// NM_008298 2.0 1.8 −1.1
1416751_a_at 53975 Ddx20 DEAD (Asp-Glu-Ala-Asp) box polypeptide 20 NM_017397 2.0 1.4 1.1
1415940_at 100494 Zfand2a zinc finger, AN1-type domain 2A NM_001159908 /// NM_133349 2.0 1.9 1.1
1420930_s_at 54366 Ctnnal1 catenin (cadherin associated protein), alpha-like 1 NM_018761 2.0 1.7 1.1
1431057_a_at 76453 Prss23 protease, serine, 23 NM_029614 2.0 1.3 1.1
1417426_at 19073 Srgn serglycin NM_011157 2.0 1.7 −1.1
1449858_at 12524 Cd86 CD86 antigen NM_019388 2.0 1.7 −1.0
1448413_at 71952 2410016O06Rik RIKEN cDNA 2410016O06 gene NM_023633 2.0 1.5 1.0
1420664_s_at 19124 Procr protein C receptor, endothelial NM_011171 2.0 1.7 −1.0
1419940_at 109260 C030018P15Rik RIKEN cDNA C030018P15 gene --- 2.0 1.9 −1.1
1437630_at 224092 Lsg1 large subunit GTPase 1 homolog (S. cerevisiae) NM_178069 2.0 1.4 1.2
1437320_s_at 22590 Xpa xeroderma pigmentosum, complementation group A NM_011728 −2.0 −1.9 −1.0
1439453_x_at 68209 Rnaseh2c ribonuclease H2, subunit C NM_026616 −2.0 −1.8 −1.1
1416053_at 16979 Lrrn1 leucine rich repeat protein 1, neuronal NM_008516 −2.0 −1.9 1.0
1429177_x_at 20671 Sox17 SRY-box containing gene 17 NM_011441 −2.0 −1.9 1.1
1419332_at 54156 Egfl6 EGF-like-domain, multiple 6 NM_019397 −2.0 −1.4 1.0
1426544_a_at 67120 Ttc14 tetratricopeptide repeat domain 14 NM_025978 /// NM_027619 −2.0 −1.8 1.2
1450803_at 18205 Ntf3 neurotrophin 3 NM_001164034 /// NM_001164035 /// NM_008742 −2.1 −1.6 −1.3
1428483_a_at 66578 Mis18a MIS18 kinetochore protein homolog A (S. pombe) NM_025642 −2.1 −1.6 −1.0
1455092_at 22680 Zfp207 zinc finger protein 207 NM_001130169 /// NM_001130170 /// NM_001130171 /// NM_011751 /// NR_045038 −2.1 −1.8 1.1
1448530_at 66355 Gmpr guanosine monophosphate reductase NM_025508 −2.1 −1.4 −1.2
1455831_at 233908 Fus fused in sarcoma NM_139149 −2.1 −1.7 −1.1
1425111_at 66673 Sorcs3 sortilin-related VPS10 domain containing receptor 3 NM_025696 −2.1 −1.3 −1.4
1451901_at 20585 Hltf helicase-like transcription factor NM_009210 /// NM_144959 −2.1 −1.7 1.0
1418266_at 11686 Alox12b arachidonate 12-lipoxygenase, 12R type NM_009659 −2.1 −1.4 1.5
1423084_at 26878 B3galt2 UDP-Gal:betaGlcNAc beta 1,3-galactosyltransferase, polypeptide 2 NM_020025 −2.1 −1.7 1.1
1438710_at 15550 Htr1a 5-hydroxytryptamine (serotonin) receptor 1A NM_008308 −2.1 −1.5 −1.2
1425175_at 227580 C1ql3 C1q-like 3 NM_153155 −2.1 −1.7 1.0
1421818_at 12053 Bcl6 B cell leukemia/lymphoma 6 NM_009744 −2.1 −1.7 −1.3
1438034_at 66302 Rmdn1 regulator of microtubule dynamics 1 NM_025476 −2.2 −1.9 1.1
1451344_at 231633 Tmem119 transmembrane protein 119 NM_146162 −2.2 −1.9 −1.0
1425344_at 67608 Narf nuclear prelamin A recognition factor NM_026272 −2.2 −1.6 −1.1
1417574_at 20315 Cxcl12 chemokine (C-X-C motif) ligand 12 NM_001012477 /// NM_013655 /// NM_021704 −2.2 −1.8 −1.2
1428052_a_at 68310 Zmym1 zinc finger, MYM domain containing 1 NM_026670 −2.2 −1.9 1.1
1427017_at 212712 Satb2 special AT-rich sequence binding protein 2 NM_139146 −2.3 1.2 −1.4
1438465_at 414758 5830428H23Rik RIKEN cDNA 5830428H23 gene NM_001001737 /// XR_105997 −2.4 −1.8 −1.2
1426552_a_at 14025 Bcl11a B cell CLL/lymphoma 11A (zinc finger protein) NM_001159289 /// NM_001159290 /// NM_001242934 /// NM_016707 −2.4 −1.7 −1.2
1424303_at 211896 Depdc7 DEP domain containing 7 NM_144804 −2.5 −1.2 −2.0
1427975_at 75668 Rasl10a RAS-like, family 10, member A NM_145216 −2.9 −2.0 −1.1
TI vs TS (44 genes)
Probeset ID Entrez Gene Gene Symbol Gene Title ReSeq Transcript ID WI vs WS TI vs TS TS vs WS
1454770_at 12426 Cckbr cholecystokinin B receptor NM_007627 1.48 2.71 −1.54
1450700_at 260409 Cdc42ep3 CDC42 effector protein (Rho GTPase binding) 3 NM_026514 1.58 2.48 1.10
1450843_a_at 12406 Serpinh1 serine (or cysteine) peptidase inhibitor, clade H, member 1 NM_001111043 /// NM_001111044 /// NM_009825 1.85 2.43 −1.38
1423614_at 100604 Lrrc8c leucine rich repeat containing 8 family, member C NM_133897 1.68 2.43 −1.25
1416897_at 80285 Parp9 poly (ADP-ribose) polymerase family, member 9 NM_030253 1.89 2.40 −1.03
1417812_a_at 16780 Lamb3 laminin, beta 3 NM_001277928 /// NM_008484 1.96 2.40 1.17
1419654_at 21887 Tle3 transducin-like enhancer of split 3, homolog of Drosophila E(spl) NM_001083927 /// NM_001083928 /// NM_009389 1.94 2.37 −1.07
1417332_at 19725 Rfx2 regulatory factor X, 2 (influences HLA class II expression) NM_009056 /// NM_027787 1.67 2.37 −1.25
1420589_at 15118 Has3 hyaluronan synthase 3 NM_008217 1.44 2.33 −1.80
1417240_at 22793 Zyx zyxin NM_011777 1.96 2.29 −1.05
1449161_at 13615 Edn2 endothelin 2 NM_007902 1.79 2.29 −1.27
1448228_at 16948 Lox lysyl oxidase NM_010728 1.10 2.27 1.59
1451794_at 319880 Tmcc3 transmembrane and coiled coil domains 3 NM_001168684 /// NM_172051 /// NM_177026 2.00 2.27 −1.04
1451751_at 73284 Ddit4l DNA-damage-inducible transcript 4-like NM_030143 1.59 2.26 −1.34
1418025_at 20893 Bhlhe40 basic helix-loop-helix family, member e40 NM_011498 1.86 2.24 −1.25
1416287_at 19736 Rgs4 regulator of G-protein signaling 4 NM_009062 1.92 2.23 −1.30
1415874_at 24063 Spry1 sprouty homolog 1 (Drosophila) NM_011896 1.42 2.21 −1.25
1451873_a_at 17129 Smad5 SMAD family member 5 NM_001164041 /// NM_001164042 /// NM_008541 1.73 2.19 −1.09
1425420_s_at 50523 Lats2 large tumor suppressor 2 NM_015771 /// NM_153382 1.97 2.17 1.04
1450350_a_at 81703 Jdp2 Jun dimerization protein 2 NM_001205052 /// NM_001205053 /// NM_030887 1.63 2.14 −1.58
1431734_a_at 67035 Dnajb4 DnaJ (Hsp40) homolog, subfamily B, member 4 NM_025926 /// NM_027287 1.95 2.14 −1.01
1448860_at 140743 Rem2 rad and gem related GTP binding protein 2 NM_080726 1.46 2.13 −1.57
1450229_at 26896 Med14 mediator complex subunit 14 NM_001048208 /// NM_012005 1.83 2.12 −1.03
1417884_at 104681 Slc16a6 solute carrier family 16 (monocarboxylic acid transporters), member 6 NM_001029842 /// NM_134038 1.35 2.12 −1.18
1453678_at 17190 Mbd1 methyl-CpG binding domain protein 1 NM_013594 1.82 2.11 1.02
1417379_at 29875 Iqgap1 IQ motif containing GTPase activating protein 1 NM_016721 1.90 2.09 −1.02
1416564_at 20680 Sox7 SRY-box containing gene 7 NM_011446 1.51 2.09 −1.30
1416360_at 170625 Snx18 sorting nexin 18 NM_130796 1.98 2.08 −1.12
1434901_at 381990 Zbtb2 zinc finger and BTB domain containing 2 NM_001033466 1.75 2.08 −1.33
1449545_at 14172 Fgf18 fibroblast growth factor 18 NM_008005 /// NR_102395 1.77 2.08 1.14
1453392_at 69863 Ttc39b tetratricopeptide repeat domain 39B NM_025782 /// NM_027238 1.58 2.05 −1.22
1450734_at 89867 Sec16b SEC16 homolog B (S. cerevisiae) NM_001159986 /// NM_033354 /// NR_027641 1.33 2.02 −1.20
1451021_a_at 12224 Klf5 Kruppel-like factor 5 NM_009769 1.48 2.02 −1.14
1418255_s_at 20807 Srf serum response factor NM_020493 1.94 2.01 −1.38
1425400_a_at 56222 Cited4 Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 4 NM_019563 1.87 2.01 1.73
1439079_a_at 59079 Erbb2ip Erbb2 interacting protein NM_001005868 /// NM_021563 1.58 2.00 −1.03
1449482_at 382522 Hist3h2ba /// Hist3h2bb-ps histone cluster 3, H2ba /// histone cluster 3, H2bb, pseudogene NM_030082 /// NM_206882 0.51 −2.03 1.29
1416174_at 26450 Rbbp9 retinoblastoma binding protein 9 NM_015754 0.54 −2.04 1.17
1451832_at 75458 Cklf chemokine-like factor NM_001037840 /// NM_001037841 /// NM_029295 /// NM_029313 0.60 −2.18 1.54
1418788_at 21687 Tek endothelial-specific receptor tyrosine kinase NM_013690 0.52 −2.26 1.01
1454858_x_at 70152 Mettl7a1 methyltransferase like 7A1 NM_027334 0.62 −2.42 1.64
1437461_s_at 67225 Rnpc3 RNA-binding region (RNP1, RRM) containing 3 NM_001038696 /// NM_026043 0.50 −2.47 1.10
1420048_at 97455 C78859 expressed sequence C78859 --- 0.61 −2.56 1.63
1456010_x_at 15208 Hes5 hairy and enhancer of split 5 (Drosophila) NM_010419 0.54 −2.63 1.74
TS vs WS (58 genes)
Probeset ID Entrez Gene Gene Symbol Gene Title RefSeq Transcript ID WI vs WS TI vs TS TS vs WS
1456515_s_at 277353 Tcfl5 transcription factor-like 5 (basic helix-loop-helix) NM_178254 1.59 −1.28 38.59
1433579_at 238257 Tmem30b transmembrane protein 30B NM_178715 1.03 −1.11 13.88
1417797_a_at 69073 1810019J16Rik RIKEN cDNA 1810019J16 gene NM_001083916 /// NM_133707 −1.02 −1.55 13.43
1422825_at 27220 Cartpt CART prepropeptide NM_001081493 /// NM_013732 −1.13 −1.15 10.15
1424525_at 225642 Grp gastrin releasing peptide NM_175012 1.27 −1.21 9.75
1416121_at 16948 Lox lysyl oxidase NM_010728 1.65 1.25 6.91
1418304_at 170677 Cdhr1 cadherin-related family member 1 NM_130878 1.28 −1.48 6.55
1427509_at 545192 Baiap3 BAI1-associated protein 3 NM_001163270 1.45 −1.53 5.96
1418941_at 93893 Pcdhb22 protocadherin beta 22 NM_053147 1.09 −1.63 5.93
1420422_at 93892 Pcdhb21 protocadherin beta 21 NM_053146 −1.28 −1.81 5.15
1417680_at 16493 Kcna5 potassium voltage-gated channel, shaker-related subfamily, member 5 NM_145983 1.33 −1.09 4.62
1417430_at 12585 Cdr2 cerebellar degeneration-related 2 NM_007672 1.56 −1.04 4.32
1422530_at 19132 Prph peripherin NM_001163588 /// NM_001163589 /// NM_013639 1.07 −1.36 4.05
1417920_at 93835 Amn amnionless NM_033603 1.74 1.32 3.90
1416627_at 20732 Spint1 serine protease inhibitor, Kunitz type 1 NM_016907 1.34 −1.53 3.58
1421396_at 18548 Pcsk1 proprotein convertase subtlisin/kexin type 1 NM_013628 1.06 −1.60 3.55
1418301_at 54139 Irf6 interferon regulatory factor 6 NM_016851 /// NM_178083 −1.65 −1.13 3.48
1449283_a_at 29857 Mapk12 mitogen-activated protein kinase 12 NM_013871 1.04 −1.18 3.33
1452270_s_at 65969 Cubn cubilin (intrinsic factor-cobalamin receptor) NM_001081084 1.92 −1.32 3.20
1449491_at 105844 Card10 caspase recruitment domain family, member 10 NM_130859 1.05 −1.27 3.19
1422586_at 13599 Ecel1 endothelin converting enzyme-like 1 NM_001277925 /// NM_021306 −1.16 −1.25 3.05
1421129_a_at 53313 Atp2a3 ATPase, Ca++ transporting, ubiquitous NM_001163336 /// NM_001163337 /// NM_016745 −1.01 −1.64 2.97
1449583_at 93891 Pcdhb20 protocadherin beta 20 NM_053145 −1.57 −1.96 2.89
1425288_at 231004 Samd11 sterile alpha motif domain containing 11 NM_001110516 /// NM_173736 1.29 1.10 2.86
1419021_at 109904 Mcf2 mcf.2 transforming sequence NM_133197 −1.38 −1.33 2.86
1418488_s_at 72388 Ripk4 receptor-interacting serine-threonine kinase 4 NM_023663 1.25 1.41 2.82
1434674_at 17101 Lyst lysosomal trafficking regulator NM_010748 −1.05 −1.35 2.68
1418373_at 56012 Pgam2 phosphoglycerate mutase 2 NM_018870 −1.39 −1.71 2.67
1426271_at 226026 Smc5 structural maintenance of chromosomes 5 NM_001252684 /// NM_001252685 /// NM_153808 1.03 −1.30 2.67
1423770_at 217353 Tmc6 transmembrane channel-like gene family 6 NM_145439 /// NM_181321 1.23 −1.11 2.56
1424581_at 217154 Stac2 SH3 and cysteine rich domain 2 NM_146028 1.06 −1.08 2.50
1425050_at 66307 Isoc1 isochorismatase domain containing 1 NM_025478 −1.06 −1.60 2.48
1435477_s_at 14130 Fcgr2b Fc receptor, IgG, low affinity IIb NM_001077189 /// NM_010187 1.67 −1.12 2.48
1417933_at 16012 Igfbp6 insulin-like growth factor binding protein 6 NM_008344 −1.31 −1.27 2.43
1437226_x_at 17357 Marcksl1 MARCKS-like 1 NM_010807 1.37 −1.16 2.39
1419517_at 72978 Cnih3 cornichon homolog 3 (Drosophila) NM_001160211 /// NM_001160212 /// NM_028408 1.23 −1.10 2.38
1424767_at 104010 Cdh22 cadherin 22 NM_174988 1.57 −1.08 2.36
1427115_at 17883 Myh3 myosin, heavy polypeptide 3, skeletal muscle, embryonic NM_001099635 1.05 −1.04 2.31
1416125_at 14229 Fkbp5 FK506 binding protein 5 NM_010220 1.10 −1.35 2.29
1460366_at 225898 Eml3 echinoderm microtubule associated protein like 3 NM_144872 −1.07 −1.23 2.28
1422552_at 67874 Rprm reprimo, TP53 dependent G2 arrest mediator candidate NM_023396 1.50 −1.44 2.23
1424451_at 235674 Acaa1b acetyl-Coenzyme A acyltransferase 1B NM_146230 1.08 1.10 2.21
1422659_at 108058 Camk2d calcium/calmodulin-dependent protein kinase II, delta NM_001025438 /// NM_001025439 /// NM_023813 1.53 −1.30 2.20
1419470_at 14696 Gnb4 guanine nucleotide binding protein (G protein), beta 4 NM_013531 1.20 −1.03 2.18
1448807_at 99296 Hrh3 histamine receptor H3 NM_133849 /// NR_102309 1.00 −1.18 2.17
1449839_at 12367 Casp3 caspase 3 NM_009810 1.93 1.51 2.16
1421505_at 27217 Mixl1 Mix1 homeobox-like 1 (Xenopus laevis) NM_013729 1.03 −1.54 2.15
1423551_at 12554 Cdh13 cadherin 13 NM_019707 −1.31 −1.22 2.13
1449837_at 66712 Spesp1 sperm equatorial segment protein 1 NM_025721 −1.14 −1.72 2.10
1419606_a_at 21955 Tnnt1 troponin T1, skeletal, slow NM_001277903 /// NM_001277904 /// NM_011618 −1.02 −1.47 2.07
1438673_at 218756 Slc4a7 solute carrier family 4, sodium bicarbonate cotransporter, member 7 NM_001033270 1.61 1.01 2.07
1424902_at 72324 Plxdc1 plexin domain containing 1 NM_001163608 /// NM_028199 −1.31 −1.14 2.06
1448635_at 14211 Smc2 structural maintenance of chromosomes 2 NM_008017 −1.45 −1.57 2.05
1426936_at 192885 /// 215866 /// 629242 /// 641366 BC005512 /// F630007L15Rik /// Gm6958 /// LOC215866 cDNA sequence BC005512 /// RIKEN cDNA F630007L15 gene /// predicted gene 6958 /// uncha XM_001479180 /// XM_001480210 /// XM_003688870 /// XM_003689442 /// XM_989008 /// XR_14 1.65 1.11 2.04
1450998_at 65020 Zfp110 zinc finger protein 110 NM_022981 1.64 1.08 2.04
1448823_at 20315 Cxcl12 chemokine (C-X-C motif) ligand 12 NM_001012477 /// NM_013655 /// NM_021704 −1.41 −1.33 −2.76
1418476_at 12931 Crlf1 cytokine receptor-like factor 1 NM_018827 −1.12 −1.05 −2.77
1427351_s_at 16019 Ighm immunoglobulin heavy constant mu --- 1.08 1.42 −3.06
Overlap (222 genes)
Probeset ID Entrez
Gene
Gene
Symbol
Gene Title RefSeq Transcript
ID
WI
vs
WS
TI
vs
TS
TS
vs
WS
1450716_at 11504 Adamts1 A disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 mo NM_009621 4.0 5.0 1.0
1419706_a_at 83397 Akap12 A kinase (PRKA) anchor protein (gravin) 12 NM_031185 3.5 3.8 −1.0
1449363_at 11910 Atf3 Activating transcription factor 3 NM_007498 46.7 33.1 −1.2
1432007_s_at 11772 Ap2a2 Adaptor-related protein complex 2, alpha 2 subunit NM_007459 2.3 2.2 1.2
1418823_at 11845 Arf6 ADP-ribosylation factor 6 NM_007481 2.5 2.0 1.0
1418250_at 80981 Arl4d ADP-ribosylation factor-like 4D NM_025404 4.5 2.6 1.1
1423420_at 11554 Adrb1 Adrenergic receptor, beta 1 NM_007419 3.1 2.3 1.0
1416077_at 11535 Adm Adrenomedullin NM_009627 2.2 3.0 −1.1
1417130_s_at 57875 Angptl4 Angiopoietin-like 4 NM_020581 4.2 2.7 1.4
1453287_at 67434 Ankrd33b Ankyrin repeat domain 33B NM_001164441 /// NM_026153/// NM_027496 2.7 2.2 −1.1
1419091_a_at 12306 Anxa2 Annexin A2 NM_007585 2.8 2.5 −1.1
1424481_s_at 494468 Armcx5 Armadillo repeat containing, X-linked 5 NM_001009575 2.5 2.1 1.2
1451340_at 214855 Arid5a AT rich interactive domain 5A (MRF1-like) NM_001172205 /// NM_001172206 /// NM_145996 /// NR_033310 3.3 4.1 −1.3
1420973_at 71371 Arid5b AT rich interactive domain 5B (MRF1-like) NM_023598 2.7 2.2 1.1
1419004_s_at 12044/// 12045/// 12047 Bcl2a1a /// Bcl2a1b /// Bcl2a1d B cell leukemia/lymphoma 2 related protein A1a /// B cell leukemia/lymphoma 2 related p NM_007534 /// NM_007536 /// NM_009742 3.1 2.6 −1.1
1416250_at 12227 Btg2 B cell translocation gene 2, anti-proliferative NM_007570 4.2 3.2 1.2
1422452_at 29810 Bag3 BCL2-associated athanogene 3 NM_013863 5.5 3.0 1.2
1423753_at 68010 Bambi BMP and activin membrane-bound inhibitor NM_026505 2.1 2.2 1.5
1437419_at 140780 Bmp2k BMP2 inducible kinase NM_080708 3.7 2.2 1.4
1422169_a_at 12064 Bdnf Brain derived neurotrophic factor NM_001048139 /// NM_001048141 /// NM_001048142 /// NM_007540 2.3 2.3 −1.4
1433956_at 12562 Cdh5 Cadherin 5 NM_009868 2.6 2.5 −1.1
1437270_a_at 56708 Clcf1 Cardiotrophin-like cytokine factor 1 NM_019952 2.4 2.1 1.0
1427844_a_at 12608 Cebpb CCAAT/enhancer binding protein (C/EBP), beta NM_009883 2.9 2.2 −1.1
1417268_at 12475 Cd14 CD14 antigen NM_009841 5.1 4.2 −1.1
1416034_at 12484 Cd24a CD24a antigen NM_009846 2.8 2.1 2.1
1423760_at 12505 Cd44 CD44 antigen NM_001039150 /// NM_001039151 /// NM_001177785 /// NM_001177786 /// NM_001177787 /// NM 6.2 4.4 −1.0
1419589_at 17064 Cd93 CD93 antigen NM_010740 3.0 3.0 −1.2
1450842_a_at 12615 Cenpa Centromere protein A NM_007681 6.2 5.2 −1.2
1427205_x_at 76380 Cep112 Centrosomal protein 112 NM_029586 /// NM_029606 /// NM_145688 2.0 2.1 1.0
1451382_at 69065 Chac1 ChaC, cation transport regulator 1 NM_026929 7.9 5.9 1.0
1419561_at 20302 Ccl3 Chemokine (C-C motif) ligand 3 NM_011337 4.5 4.6 −1.3
1419209_at 14825 Cxcl1 Chemokine (C-X-C motif) ligand 1 NM_008176 9.4 8.4 1.0
1424143_a_at 67177 Cdt1 Chromatin licensing and DNA replication factor 1 NM_026014 2.1 2.1 1.1
1431166_at 12648 Chd1 Chromodomain helicase DNA binding protein 1 NM_007690 2.2 2.2 1.0
1424409_at 71908 Cldn23 Claudin 23 NM_027998 2.2 2.1 −1.0
1452414_s_at 108673 Ccdc86 Coiled-coil domain containing 86 NM_023731 4.8 3.5 1.2
1452035_at 12826 Col4a1 Collagen, type IV, alpha 1 NM_009931 2.8 2.2 1.3
1419483_at 12267 C3ar1 Complement component 3a receptor 1 NM_009779 3.0 2.5 −1.1
1416953_at 14219 Ctgf Connective tissue growth factor NM_010217 3.5 3.7 −1.2
1434618_at 233490 Crebzf CREB/ATF bZIP transcription factor NM_145151 /// NR_073436 /// NR_073437 /// NR_073438 −2.8 −2.5 −1.1
1433733_a_at 12952 Cry1 Cryptochrome 1 (photolyase-like) NM_007771 2.7 2.4 −1.0
1423622_a_at 56706 Ccnl1 Cyclin L1 NM_001025442 /// NM_001025443 /// NM_019937 2.3 2.1 −1.1
1421679_a_at 12575 Cdkn1a Cyclin-dependent kinase inhibitor 1A (P21) NM_001111099 /// NM_007669 4.1 3.0 1.2
1438133_a_at 16007 Cyr61 Cysteine rich protein 61 NM_010516 14.5 21.3 1.1
1422533_at 13121 Cyp51 Cytochrome P450, family 51 NM_020010 2.8 2.1 1.1
1455372_at 208922 Cpeb3 Cytoplasmic polyadenylation element binding protein 3 NM_198300 2.6 2.0 −1.0
1449931_at 67579 Cpeb4 Cytoplasmic polyadenylation element binding protein 4 NM_026252 2.8 2.1 1.2
1416814_at 21841 Tia1 Cytotoxic granule-associated RNA binding protein 1 NM_001164078 /// NM_001164079 /// NM_011585 −2.2 −2.1 1.1
1448471_a_at 13024 Ctla2a Cytotoxic T lymphocyte-associated protein 2 alpha NM_001145799 /// NM_007796 4.4 3.6 −1.2
1452352_at 13025 Ctla2b Cytotoxic T lymphocyte-associated protein 2 beta NM_001145801 /// NM_007797 2.6 2.5 −1.1
1417937_at 59036 Dact1 Dapper homolog 1, antagonist of beta-catenin (xenopus) NM_001190466 /// NM_021532 2.5 3.2 1.2
1426081_a_at 13371 Dio2 Deiodinase, iodothyronine, type II NM_010050 3.0 2.8 1.1
1417516_at 13198 Ddit3 DNA-damage inducible transcript 3 NM_007837 2.4 2.1 1.0
1416756_at 81489 Dnajb1 DnaJ (Hsp40) homolog, subfamily B, member 1 NM_018808 5.5 5.7 −1.4
1448830_at 19252 Dusp1 Dual specificity phosphatase 1 NM_013642 2.7 4.0 −1.2
1418401_a_at 70686 Dusp16 Dual specificity phosphatase 16 NM_001048054 /// NM_130447/// NM_181320 3.3 3.1 −1.0
1415834_at 67603 Dusp6 Dual specificity phosphatase 6 NM_026268 2.1 3.0 −1.7
1417065_at 13653 Egr1 Early growth response 1 NM_007913 2.6 4.3 −2.0
1427683_at 13654 Egr2 Early growth response 2 NM_010118 17.4 22.0 −2.3
1449977_at 13656 Egr4 Early growth response 4 NM_020596 2.3 2.2 −1.4
1416529_at 13730 Emp1 Epithelial membrane protein 1 NM_010128 7.4 5.7 1.1
1416129_at 74155 Errfi1 ERBB receptor feedback inhibitor 1 NM_133753 3.0 2.0 −1.0
1418294_at 54357 Epb4.1l4b Erythrocyte protein band 4.1-like 4b NM_019427 2.5 2.6 1.0
1418635_at 27049 Etv3 ets variant gene 3 NM_001083318 /// NM_012051 4.3 2.3 1.0
1441023_at 67204 Eif2s2 Eukaryotic translation initiation factor 2, subunit 2 (beta) NM_026030 2.7 2.1 −1.0
1417562_at 13685 Eif4ebp1 Eukaryotic translation initiation factor 4E binding protein 1 NM_007918 3.8 2.9 1.2
1438427_at 67544 Fam120b Family with sequence similarity 120, member B NM_024203 /// NR_033586 3.4 2.4 1.3
1423100_at 14281 Fos FBJ osteosarcoma oncogene NM_010234 11.4 20.2 −1.8
1422134_at 14282 Fosb FBJ osteosarcoma oncogene B NM_008036 8.9 6.6 −1.1
1451264_at 319710 Frmd6 FERM domain containing 6 NM_028127 4.3 3.2 −1.2
1418534_at 57265 Fzd2 frizzled homolog 2 (Drosophila) NM_020510 −2.5 −2.3 1.1
1450135_at 14365 Fzd3 frizzled homolog 3 (Drosophila) NM_021458 3.2 2.7 1.0
1419301_at 14366 Fzd4 frizzled homolog 4 (Drosophila) NM_008055 2.9 3.0 −1.0
1419322_at 13998 Fgd6 FYVE, RhoGEF and PH domain containing 6 NM_053072 2.7 2.5 1.1
1422542_at 23890 Gpr34 G protein-coupled receptor 34 NM_011823 −2.5 −2.7 1.1
1460275_at 14748 Gpr3 G-protein coupled receptor 3 NM_008154 2.5 2.0 1.0
1420394_s_at 14727 /// 14728 Gp49a /// Lilrb4 Glycoprotein 49 A /// leukocyte immunoglobulin-like receptor, subfamily B, member 4 NM_008147 /// NM_013532 4.1 2.9 1.0
1424825_a_at 14663 Glycam1 Glycosylation dependent cell adhesion molecule 1 NM_008134 2.5 2.0 −1.0
1449519_at 13197 Gadd45a Growth arrest and DNA-damage-inducible 45 alpha NM_007836 4.4 3.7 −1.2
1449773_s_at 17873 Gadd45b Growth arrest and DNA-damage-inducible 45 beta NM_008655 11.7 6.5 1.0
1453851_a_at 23882 Gadd45g Growth arrest and DNA-damage-inducible 45 gamma NM_011817 10.8 6.5 1.1
1426063_a_at 14579 Gem GTP binding protein (gene overexpressed in skeletal muscle) NM_010276 8.3 10.1 1.0
1423143_at 69237 Gtpbp4 GTP binding protein 4 NM_027000 2.9 2.2 1.1
1420499_at 14528 Gch1 GTP cyclohydrolase 1 NM_008102 2.3 2.0 −1.4
1430295_at 14674 Gna13 Guanine nucleotide binding protein, alpha 13 NM_010303 2.0 2.1 1.1
1423566_a_at 15505 Hsph1 Heat shock 105kDa/110kDa protein 1 NM_013559 3.8 3.2 −1.2
1425964_x_at 15507 Hspb1 Heat shock protein 1 NM_013560 10.7 15.2 −1.2
1422579_at 15528 Hspe1 Heat shock protein 1 (chaperonin 10) NM_008303 2.6 2.1 1.0
1452388_at 193740 Hspa1a Heat shock protein 1A NM_010479 13.9 17.6 −1.4
1427126_at 15511 Hspa1b Heat shock protein 1B NM_010478 12.9 17.6 −1.5
1449872_at 56534 Hspb3 Heat shock protein 3 NM_019960 2.7 2.2 −1.0
1431182_at 15481 Hspa8 Heat shock protein 8 NM_031165 4.4 4.6 −1.4
1425378_at 235439 Herc1 Hect (homologous to the E6-AP (UBE3A) carboxyl terminus) domain and RCC1 (CHC1)-like do NM_145617 3.9 3.2 1.3
1417541_at 15201 Hells Helicase, lymphoid specific NM_008234 2.7 2.4 1.3
1448239_at 15368 Hmox1 Heme oxygenase (decycling) 1 NM_010442 7.1 5.3 1.3
1418350_at 15200 Hbegf Heparin-binding EGF-like growth factor NM_010415 5.5 3.2 1.4
1452534_a_at 97165 Hmgb2 High mobility group box 2 NM_008252 3.2 3.4 1.0
1435866_s_at 319162 Hist3h2a Histone cluster 3, H2a NM_178218 −2.0 −2.6 1.3
1419905_s_at 15446 Hpgd Hydroxyprostaglandin dehydrogenase 15 (NAD) NM_008278 −2.7 −2.2 1.3
1416442_at 15936 Ier2 Immediate early response 2 NM_010499 7.4 6.6 −1.0
1417612_at 15939 Ier5 Immediate early response 5 NM_010500 3.8 2.8 −1.4
1437103_at 319765 Igf2bp2 Insulin-like growth factor 2 mRNA binding protein 2 NM_183029 3.3 2.0 −1.1
1424067_at 15894 Icam1 Intercellular adhesion molecule 1 NM_010493 2.2 2.3 −1.3
1416067_at 15982 Ifrd1 Interferon-related developmental regulator 1 NM_013562 3.7 2.4 1.1
1426597_s_at 212632 Iffo2 Intermediate filament family orphan 2 NM_001205173 /// NM_183148 2.5 2.0 1.1
1417409_at 16476 Jun Jun oncogene NM_010591 5.8 4.2 1.4
1449117_at 16478 Jund Jun proto-oncogene related gene d NM_010592 2.1 2.1 1.1
1415899_at 16477 Junb Jun-B oncogene NM_008416 3.2 4.1 −1.7
1425270_at 16561 Kif1b kinesin family member 1B NM_008441 /// NM_207682 2.5 2.6 −1.2
1416029_at 21847 Klf10 Kruppel-like factor 10 NM_013692 3.1 2.6 −1.4
1417394_at 16600 Klf4 Kruppel-like factor 4 (gut) NM_010637 2.4 5.9 1.0
1418280_at 23849 Klf6 Kruppel-like factor 6 NM_011803 4.7 5.5 1.1
1439479_at 226413 Lct Lactase NM_001081078 −2.5 −2.2 −1.0
1421654_a_at 16905 Lmna Lamin A NM_001002011 /// NM_001111102 /// NM_019390 5.1 4.0 1.2
1426808_at 16854 Lgals3 Lectin, galactose binding, soluble 3 NM_001145953 /// NM_010705 4.7 3.9 −1.1
1433842_at 16978 Lrrfip1 Leucine rich repeat (in FLII) interacting protein 1 NM_001111311 /// NM_001111312 /// NM_008515 6.6 5.2 1.0
1422725_at 17152 Mak Male germ cell-associated kinase NM_001145802 /// NM_001145803 /// NM_008547 3.3 4.1 −1.0
1429170_a_at 17764 Mtf1 Metal response element binding transcription factor 1 NM_008636 4.5 4.8 1.1
1451612_at 17748 Mt1 Metallothionein 1 NM_013602 2.8 3.0 1.0
1419254_at 17768 Mthfd2 Methylenetetrahydrofolate dehydrogenase (NAD+ dependent), methenyltetrahydrofolate cycl NM_008638 3.8 2.8 1.0
1434364_at 53859 Map3k14 Mitogen-activated protein kinase kinase kinase 14 NM_016896 2.4 2.2 1.0
1424942_a_at 17869 Myc Myelocytomatosis oncogene NM_001177352 /// NM_001177353 /// NM_001177354 /// NM_010849 4.0 3.8 1.1
1448503_at 17210 Mcl1 Myeloid cell leukemia sequence 1 NM_008562 6.1 4.8 1.1
1418589_a_at 17349 Mlf1 Myeloid leukemia factor 1 NM_001039543 /// NM_010801 3.4 3.1 −1.1
1422818_at 18003 Nedd9 Neural precursor cell expressed, developmentally down-regulated gene 9 NM_001111324 /// NM_017464 3.6 3.8 1.0
1420720_at 53324 Nptx2 Neuronal pentraxin 2 NM_016789 7.2 3.0 1.0
1417930_at 17937 Nab2 Ngfi-A binding protein 2 NM_001122895 /// NM_008668 2.9 2.3 −1.2
1417483_at 80859 Nfkbiz Nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, zeta NM_001159394 /// NM_001159395 /// NM_030612 6.4 4.6 1.4
1418932_at 18030 Nfil3 Nuclear factor, interleukin 3, regulated NM_017373 5.9 7.1 −1.4
1428083_at 66961 Neat1 Nuclear paraspeckle assembly transcript 1 (non-protein coding) NR_003513 2.2 2.5 −1.2
1416505_at 15370 Nr4a1 Nuclear receptor subfamily 4, group A, member 1 NM_010444 2.1 3.6 −2.4
1436780_at 108155 Ogt O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N-acetylglucosamine:polypeptide- NM_139144 −2.3 −2.2 1.2
1418674_at 18414 Osmr Oncostatin M receptor NM_011019 7.2 4.1 1.3
1423174_a_at 58220 Pard6b par-6 (partitioning defective 6) homolog beta (C. elegans) NM_021409 3.4 2.6 −1.1
1422324_a_at 19227 Pthlh Parathyroid hormone-like peptide NM_008970 3.5 4.0 −1.1
1417372_a_at 67245 Peli1 Pellino 1 NM_023324 2.2 2.2 1.2
1419006_s_at 93834 Peli2 Pellino 2 NM_033602 2.1 2.1 −1.0
1449851_at 18626 Per1 Period circadian clock 1 NM_001159367 /// NM_011065 2.5 2.3 1.1
1417602_at 18627 Per2 Period circadian clock 2 NM_011066 2.5 2.8 −1.6
1420715_a_at 19016 Pparg Peroxisome proliferator activated receptor gamma NM_001127330 /// NM_011146 3.4 2.1 1.0
1421811_at 21825 Thbs1 Thrombospondin 1 NM_011580/// NM_013753 13.7 8.0 1.3
1421917_at 18595 Pdgfra Platelet derived growth factor receptor, alpha polypeptide NM_001083316 /// NM_011058 −2.0 −2.0 1.1
1418835_at 21664 Phlda1 Pleckstrin homology-like domain, family A, member 1 NM_009344 3.4 3.4 −1.2
1434496_at 12795 Plk3 Polo-like kinase 3 NM_013807 2.2 2.4 −1.0
1429456_a_at 26939 Polr3e Polymerase (RNA) III (DNA directed) polypeptide E NM_001164096 /// NM_025298 2.5 2.4 1.4
1424874_a_at 19205 Ptbp1 Polypyrimidine tract binding protein 1 NM_001077363 /// NM_008956 2.6 2.0 1.1
1425341_at 16527 Kcnk3 Potassium channel, subfamily K, member 3 NM_010608 3.1 2.1 −1.2
1431213_a_at 67527 /// 100041932 Gm3579 /// LOC67527 Predicted gene 3579 /// murine leukemia retrovirus XM_001477842 2.5 2.1 −1.2
1433668_at 108767 Pnrc1 Proline-rich nuclear receptor coactivator 1 NM_001033225 −2.1 −2.1 −1.0
1424208_at 19219 Ptger4 Prostaglandin E receptor 4 (subtype EP4) NM_001136079 /// NM_008965 4.6 2.6 1.4
1417262_at 19225 Ptgs2 Prostaglandin-endoperoxide synthase 2 NM_011198 8.5 3.3 −1.3
1448325_at 17872 Ppp1r15a Protein phosphatase 1, regulatory (inhibitor) subunit 15A NM_008654 4.2 4.7 1.0
1429715_at 71978 Ppp2r2a Protein phosphatase 2 (formerly 2A), regulatory subunit B (PR 52), alpha isoform NM_001205188 /// NM_028032 2.8 2.1 1.1
1449249_at 54216 Pcdh7 Protocadherin 7 NM_001122758 /// NM_018764 3.0 2.7 −1.2
1435458_at 18712 Pim1 Proviral integration site 1 NM_008842 5.6 2.5 −1.2
1431724_a_at 70839 P2ry12 Purinergic receptor P2Y, G-protein coupled 12 NM_027571 −2.8 −2.4 1.1
1427931_s_at 216134 Pdxk Pyridoxal (pyridoxine, vitamin B6) kinase NM_172134 2.4 2.0 1.1
1417273_at 27273 Pdk4 Pyruvate dehydrogenase kinase, isoenzyme 4 NM_013743 3.0 2.2 1.1
1426452_a_at 75985 Rab30 RAB30, member RAS oncogene family NM_029494 2.3 2.1 −1.1
1448414_at 19355 Rad1 RAD1 homolog (S. pombe) NM_011232 −2.1 −2.1 1.0
1418892_at 80837 Rhoj ras homolog gene family, member J NM_023275 3.4 2.2 1.3
1423854_a_at 68939 Rasl11b RAS-like, family 11, member B NM_026878 2.0 2.6 −1.6
1422562_at 56437 Rrad Ras-related associated with diabetes NM_019662 14.6 4.5 1.8
1426037_a_at 19734 Rgs16 regulator of G-protein signaling 16 NM_011267 2.3 2.0 1.3
1452359_at 100532 Rell1 RELT-like 1 NM_145923 2.4 2.2 1.1
1420710_at 19696 Rel Reticuloendotheliosis oncogene NM_009044 3.4 2.6 −1.1
1416700_at 74194 Rnd3 Rho family GTPase 3 NM_028810 3.2 3.3 −1.0
1438502_x_at 20068 Rps17 Ribosomal protein S17 NM_009092 3.1 2.8 −1.1
1427299_at 110651 Rps6ka3 Ribosomal protein S6 kinase polypeptide 3 NM_148945 2.3 2.0 −1.1
1427932_s_at 71719 /// 71739 /// 319269 1200003I10Rik /// 1200015M12Rik /// A130040M12Rik RIKEN cDNA 1200003I10 gene /// RIKEN cDNA 1200015M12 gene /// RIKEN cDNA A130040M12 gen NR_002860 3.7 3.8 −1.2
1451415_at 69068 1810011O10Rik RIKEN cDNA 1810011O10 gene NM_026931 2.3 2.5 1.3
1428552_at 66520 2610001J05Rik RIKEN cDNA 2610001J05 gene NM_183258 /// NR_024619 −2.1 −2.2 1.1
1416355_at 19655 Rbmx RNA binding motif protein, X chromosome NM_001166623 /// NM_011252 /// NR_029425 −2.1 −2.1 −1.2
1424704_at 12393 Runx2 Runt related transcription factor 2 NM_001145920 /// NM_001146038 /// NM_001271627 /// NM_001271630 /// NM_001271631 /// NM 2.6 2.3 −1.1
1419149_at 18787 Serpine1 Serine (or cysteine) peptidase inhibitor, clade E, member 1 NM_008871 3.2 3.0 −1.1
1429650_at 74178 Stk40 Serine/threonine kinase 40 NM_001145827 /// NM_028800 3.4 2.4 1.0
1417406_at 55942 Sertad1 SERTA domain containing 1 NM_018820 2.9 2.4 −1.2
1425139_at 230784 Sesn2 Sestrin 2 NM_144907 2.7 2.3 1.0
1448170_at 20439 Siah2 Seven in absentia 2 NM_009174 2.6 2.6 −1.1
1433674_a_at 83673 Snhg1 Small nucleolar RNA host gene (non-protein coding) 1 NR_002896 4.6 3.6 1.2
1428529_at 72655 Snhg5 Small nucleolar RNA host gene 5 NR_040721 2.6 2.2 1.1
1428776_at 75750 Slc10a6 Solute carrier family 10 (sodium/bile acid cotransporter family), member 6 NM_029415 5.4 5.4 −1.2
1420697_at 65221 Slc15a3 Solute carrier family 15, member 3 NM_023044 2.6 2.6 −1.2
1438824_at 20515 Slc20a1 Solute carrier family 20, member 1 NM_001159593 /// NM_015747 2.3 2.7 1.1
1422786_at 22782 Slc30a1 Solute carrier family 30 (zinc transporter), member 1 NM_009579 2.6 2.4 1.0
1420405_at 28250 Solute carrier organic anion transporter family, member 1a4 NM_030687 −2.6 −2.3 −1.1
1422256_at 20606 Sstr2 Somatostatin receptor 2 NM_001042606 /// NM_009217 3.4 2.8 −1.1
1451596_a_at 20698 Sphk1 Sphingosine kinase 1 NM_001172472 /// NM_001172473 /// NM_001172475 /// NM_011451 /// NM_025367 2.5 2.7 −1.3
1420150_at 74646 Spsb1 splA/ryanodine receptor domain and SOCS box containing 1 NM_029035 2.6 2.4 −1.2
1436584_at 24064 Spry2 Sprouty homolog 2 (Drosophila) NM_011897 3.5 2.4 −1.2
1449109_at 216233 Socs2 Suppressor of cytokine signaling 2 NM_001168655 /// NM_001168656 /// NM_001168657 /// NM_007706 2.1 2.3 −1.1
1456212_x_at 12702 Socs3 Suppressor of cytokine signaling 3 NM_007707 11.6 13.1 −1.3
1434089_at 104027 Synpo Synaptopodin NM_001109975 /// NM_177340 2.3 2.5 −1.1
1430271_x_at 75316 Taf1d TATA box binding protein (Tbp)-associated factor, RNA polymerase I, D NM_026541 /// NM_027261 /// NM_029248 /// NR_028401 2.1 2.3 1.1
1452161_at 99929 Tiparp TCDD-inducible poly(ADP-ribose) polymerase NM_178892 4.8 2.8 1.2
1416342_at 21923 Tnc Tenascin C NM_011607 5.8 4.3 1.2
1424012_at 78802 Ttc30a1 Tetratricopeptide repeat domain 30A1 NM_030188 −2.4 −2.1 1.0
1418547_at 21789 Tfpi2 Tissue factor pathway inhibitor 2 NM_009364 2.6 2.0 −1.1
1454018_at 24086 Tlk2 Tousled-like kinase 2 (Arabidopsis) NM_001112705 /// NM_011903 2.6 2.5 1.2
1436854_at 22064 Trpc2 Transient receptor potential cation channel, subfamily C, member 2 NM_001109897 /// NM_011644 −2.2 −2.4 1.1
1423289_a_at 66282 Tma16 Translation machinery associated 16 homolog (S. cerevisiae) NM_025465 2.5 2.2 1.1
1424880_at 211770 Trib1 Tribbles homolog 1 (Drosophila) NM_144549 3.9 3.8 −1.3
1430576_at 22019 Tpp2 Tripeptidyl peptidase II NM_009418 2.5 2.4 1.2
1416431_at 67951 Tubb6 Tubulin, beta 6 class V NM_026473 5.9 6.4 −1.0
1418572_x_at 27279 Tnfrsf12a Tumor necrosis factor receptor superfamily, member 12a NM_001161746 /// NM_013749 7.0 6.7 −1.2
1456094_at 72344 Usp36 Ubiquitin specific peptidase 36 NM_001033528 3.1 2.4 −1.1
1452385_at 99526 Usp53 Ubiquitin specific peptidase 53 NM_133857 3.1 2.3 1.1
1436882_at 66177 Ubl5 Ubiquitin-like 5 NM_025401 2.1 2.1 1.2
1454842_a_at 97884 B3galnt2 UDP-GalNAc:betaGlcNAcbeta 1,3-galactosaminyltransferase, polypeptide 2 NM_178640 −2.9 −3.2 1.2
1420994_at 108105 B3gnt5 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 5 NM_001159407 /// NM_001159408 /// NM_054052 2.5 2.8 −1.2
1434606_at 13867 Erbb3 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) NM_010153 −3.5 −2.3 −1.4
1418936_at 17133 Maff v-maf musculoaponeurotic fibrosarcoma oncogene family, protein F (avian) NM_010755 6.0 5.6 −1.1
1455812_x_at 246154 Vasn vasorin NM_139307 2.3 2.1 1.1
1456292_a_at 22352 Vim Vimentin NM_011701 2.5 2.1 −1.1
1434744_at 230734 Yrdc yrdC domain containing (E.coli) NM_153566 2.1 2.1 1.0
1422570_at 22632 Yy1 YY1 transcription factor NM_009537 2.2 2.1 1.0
1425305_at 114565 Zbtb21 Zinc finger and BTB domain containing 21 NM_001081684 /// NM_001081685 /// NM_175428 2.4 2.1 1.0
1452519_a_at 22695 Zfp36 Zinc finger protein 36 NM_011756 4.1 5.2 −1.1
1424974_at 232854 Zfp418 Zinc finger protein 418 NM_146179 −2.3 −2.3 −1.1
1449946_a_at 68040 Zfp593 Zinc finger protein 593 NM_024215 2.5 2.4 −1.1
1452623_at 268670 Zfp759 Zinc finger protein 759 NM_172392 −2.1 −2.4 1.3
1427539_a_at 52696 Zwint ZW10 interactor NM_025635 4.9 4.1 1.2
Overlap (1 genes)
RefSeq transcript ID WI vs WS TI vs TS TS vs WS
NM_001276684 /// NM_018790 6.15 8.25 −2.46
Overlap (2 genes)
Gene
symbol
Gene title RefSeq transcript ID WI vs WS TI vs TS TS vs WS
Sox11 SRY-box containing gene 11 NM_009234 3.51 −1.37 3.32
Upp1 uridine phosphorylase 1 NM_001159401 /// NM_001159402 /// NM_009477 2.14 1.04 2.14
Overlap (3 genes)
Probeset ID Entrez
gene
Gene
symbol
gene title RefSeq transcript ID WI vs
WS
TI vs
TS
TS vs
WS
1418160_at 22652 Mkrn3 makorin, ring finger protein, 3 NM_011746 −1.47 −2.05 5.40
1418475_at 20277 Scnn1b sodium channel, nonvoltage-gated 1 beta NM_001272023 /// NM_011325 /// NR_073548 −1.20 −2.61 3.66
1419663_at 18295 Ogn osteoglycin NM_008760 −1.30 −2.81 5.70

Footnotes

CONFLICT OF INTEREST

The authors declare that there is no conflict of interest.

REFERENCES

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