Table 2.
Gene ontology enrichment analysis for HSP990 treated mice.
| comparison | regulation | genes | regulators (1: ChEA, 2: ENCODE) | pathways (1: WIKIPathways, 2: Reactome) | gene ontologies (biological process) | kinases | chromatin marks |
|---|---|---|---|---|---|---|---|
| WTvehicle vs. HSP990 | up | 479 | 1: HSF1 382.44, ESR1 177.22, CLOCK 143.11, EP300 131.96, TCF21 130.52: HSF1 67.04, TCF12 56.90, MYOD1 53.53, GATA3 38.37, TCF3 36.89 | 1: Focal Adhesion 26.64, Inflammatory Response Pathway 16.87, IL-2 Signaling Pathway 9.78, Apoptosis-related network due to altered Notch3 in ovarian cancer 9.42, Type II interferon signaling 8.592: Extracellular matrix organization 61.98, Collagen biosynthesis and modifying enzymes 32.3, Attenuation phase (of HSF1) 25.24, HSF1 activation 24.29, Scavenging by Class A Receptors 12.71 | extracellular matrix organization 96.51, collagen fibril organization 43.4, protein folding 43.24, response to wounding 23.12, response to acid chemical 19.93 | IRAK4 158.7KSR1 83.98CDK8 72.45BMPR2 62.38FGFR1 42.72 | H3K27me3 37.46H3K27ac 28.67H3K4me1 26.28 |
| down | 195 | 1: CLOCK 95.44, TAF7L 90.88, SOX2 60.96, FOXP2 57.93, TCFAP2C 51.392: RFX5 18.54, POLR2A 13.64, E2F1 13.31, EP300 10.71, MAZ 10.24 | 1: not significant2: not significant | response to peptide 7.13, organic acid transport 6.77, cellular response to oxidative stress 6.68, positive regulation of p38MAPK cascade 6.62, negative regulation of lipid storage 5.48 | ILK 24.46IRAK4 24.10IGF1R 16.38HUNK 14.21KSR2 13.27 | H3K4me1 13.05H3K27me3 10.84H3K4me3 9.79 | |
| R6/2vehicle vs. HSP990 | up | 149 | 1: HSF1 232.59, CLOCK 51.98, TRIM28 36.67, SUZ12 35.25, E2F1 32.962: HSF1 53.66, STAT2 10.42, STAT1 10.03, EP300 9.31, FOSL1 9.24 | 1: IL-4 Signaling Pathway 6.42, Apoptosis Modulation and Signaling 6.14Adipogenesis 6.06, MAPK Signaling Pathway 5.35, SIDS Susceptibility Pathways 5.122: HSF1 activation 39.15, Attenuation phase (of HSF1) 39.11 | protein folding 32.7, regulation of apoptotic signaling pathway 13.91, negative regulation of phosphorylation 12.27, regulation of cytokine production 11.32, response to interferon-alpha 8.11 | CDK8 34.46ILK 20.06ROCK2 18.68IRAK4 13.52ROCK1 13.48 | H3K4me3 13.07H3K4me1 8.03H4K20me1 6.73 |
| down | 249 | 1: CLOCK 101.11, NANOG 80.97, ESR1 78.05, MTF2 70.52, PPARG 66.172: TCF12 15.54, CTCF 15.46, NFIC 14.83, ZC3H11A 14.13, UBTF 13.55 | 1: Adipogenesis 11.53, Signaling Pathways in Glioblastoma 7.63, EGF/EGFR Signaling Pathway 5.48, MAPK Signaling Pathway 5.472: Signaling by EGFR 6.47, Signalling by NGF 6.4, Downstream signaling of activated FGFR 6.18, Signaling by ERBB2 6.04, Signaling by FGFR 6.03 | cellular response to nitrogen compound 15.21, regulation of vasculature development 13.83, positive regulation of lipase activity 13.57, Ras protein signal transduction 12.82, positive regulation of reactive oxygen species metabolic process 12.41 | IGF1R 37.05KSR2 33.07IRAK4 31.62HUNK 24.12ROCK2 10.21 | H3K27me3 38.44H3K4me1 33.46H3K9me3 12.79 | |
| Hsf1 −/− vehicle vs. HSP990 | up | 72 | 1: TAF7L 47.7, ATF3 43.03, STAT3 42.39, SOX2 36.48, E2F1 35.422: CEBPB 47.9, CHD1 28.94, JUN 26.57, MAX 22.46, FOSL2 21.12 | 1: Hypertrophy Model 14.84, MAPK signaling pathway 6.282: PERK regulates gene expression 13.76, ATF4 activates genes 13.62, Amino acid transport across the plasma membrane 13.13, Amino acid synthesis and interconversion (transamination) 9.97, Unfolded Protein Response (UPR) 6.99 | response to endoplasmic reticulum stress 17.21, response to unfolded protein 17.1, amino acid transmembrane transport 16.99, anion transmembrane transport 16.72, apoptotic signaling pathway 16.07 | KSR1 38.98EGFR 30.53ALK 24.9IRAK4 21.98SNRK 16.38 | H3K36me3 10.33H3K4me1 8.64H3K27me3 7.21 |
| down | 40 | 1: KLF4/5/2 22.37, SMAD4 18.72, SMARCA4 18.57, SMAD3 16.92, ZFP281 15.52: not significant | 1: Striated Muscle Contraction 8.062: Muscle contraction 10.87, Signaling by NOTCH4 5.39, | negative regulation of ERK1 and ERK2 cascade 9.92, actin-myosin filament sliding 9.45, negative regulation of intracellular signal transduction 9.41, cellular response to fluid shear stress 9.0, regulation of endothelial cell differentiation 8.77 | KSR2 7.91 | H3K27me3 6.32 |
Upstream regulators were predicted using the ChIP-x Enrichment Analysis (1: ChEA) and ENCODE transcription factor ChIP-seq database 2015 (2: ENCODE). Chromatin marks were predicted using the ENCODE histone modifications database 2015. Only the top non-redundant significantly enriched terms followed by their combined score are shown. See also Tables S3, S4, S5, S7 and S9.