Table 1.
EGF responsive genes in the SCN are involved in diverse cellular processes and potentially regulated by diverse transcription factors
| Gene group | Attribute class | Attribute | p ENRICH | p ENRICH(FDR) | No. of genes | GFRAC | AFRAC | ENRICH | p M(LOCAL) | p M(GLOBAL) |
| Any EGF effect | GO | Cell differentiation | 3.E-03 | 0.08 | 7 | 0.1 | 0.3 | 3.4 | 0.02 | 0.06 |
| Protein kinase activity | 0.01 | 0.10 | 10 | 0.2 | 0.2 | 2.4 | 0.03 | 0.08 | ||
| Protein serine/threonine kinase activity | 2.E-03 | 0.08 | 10 | 0.2 | 0.2 | 2.8 | 0.01 | 0.06 | ||
| PAINT | ATF3 | 0.02 | 0.16 | 5 | 0.1 | 0.3 | 2.9 | 0.02 | 0.52 | |
| CREB | 4.E-03 | 0.06 | 9 | 0.1 | 0.3 | 2.7 | 4.E-03 | 0.10 | ||
| CREBATF | 3.E-03 | 0.06 | 5 | 0.1 | 0.5 | 4.3 | 0.04 | 0.59 | ||
| CRE-BP1:c-Jun | 0.01 | 0.14 | 7 | 0.1 | 0.3 | 2.6 | 0.02 | 0.31 | ||
| CONS | V$AP1_2 | 0.02 | 0.90 | 71 | 0.8 | 0.1 | 1.1 | 0.03 | 0.11 | |
| V$AP1_C | 1.E-03 | 0.16 | 53 | 0.6 | 0.2 | 1.4 | 2.E-03 | 0.06 | ||
| V$CEBP_Q2 | 0.01 | 0.54 | 32 | 0.4 | 0.2 | 1.4 | 0.01 | 0.03 | ||
| V$CEBP_Q2_01 | 0.03 | 0.90 | 61 | 0.7 | 0.1 | 1.2 | 0.05 | 0.06 | ||
| V$CEBP_Q3 | 2.E-03 | 0.19 | 69 | 0.8 | 0.1 | 1.2 | 2.E-03 | 0.02 | ||
| V$CEBPGAMMA_Q6 | 0.03 | 0.90 | 26 | 0.3 | 0.2 | 1.4 | 0.05 | 0.07 | ||
| V$OCT1_07 | 0.02 | 0.90 | 10 | 0.1 | 0.2 | 2.0 | 0.05 | 0.23 | ||
| V$RORA1_01 | 7.E-05 | 0.02 | 21 | 0.2 | 0.3 | 2.3 | 3.E-04 | 2.E-03 | ||
| V$RORA2_01 | 0.01 | 0.54 | 6 | 0.1 | 0.4 | 3.1 | 0.06 | 0.19 | ||
| Circ. | SCN circadian genes [17] | 0.04 | - | 16 | 0.1 | 0.4 | 1.5 | 0.02 | - | |
| EGF:CT | GO | Cell differentiation | 1.E-03 | 0.06 | 6 | 0.1 | 0.2 | 4.5 | 0.01 | 0.05 |
| interaction | PAINT | c-Ets-1/68 | 0.07 | 0.36 | 8 | 0.1 | 0.2 | 1.8 | 0.06 | 0.13 |
| CREB | 0.01 | 0.10 | 7 | 0.1 | 0.2 | 2.7 | 0.01 | 0.11 | ||
| CREBATF | 8.E-04 | 0.02 | 5 | 0.1 | 0.5 | 5.7 | 0.02 | 0.60 | ||
| CRE-BP1:c-Jun | 0.01 | 0.10 | 6 | 0.1 | 0.3 | 3.0 | 0.01 | 0.23 | ||
| E2F | 0.03 | 0.20 | 5 | 0.1 | 0.2 | 2.7 | 0.02 | 0.28 | ||
| CONS | V$AP1_C | 2.E-04 | 0.03 | 41 | 0.7 | 0.1 | 1.5 | 2.E-03 | 0.05 | |
| V$CEBP_Q2 | 2.E-03 | 0.11 | 26 | 0.4 | 0.1 | 1.7 | 0.01 | 0.07 | ||
| V$CEBP_Q3 | 5.E-03 | 0.26 | 49 | 0.8 | 0.1 | 1.2 | 0.01 | 0.09 | ||
| V$CETS1P54_01 | 0.03 | 0.71 | 46 | 0.7 | 0.1 | 1.2 | 0.05 | 0.13 | ||
| V$CREBP1_Q2 | 0.03 | 0.71 | 8 | 0.1 | 0.2 | 2.1 | 0.04 | 0.36 | ||
| V$ER_Q6_02 | 0.02 | 0.69 | 30 | 0.5 | 0.1 | 1.4 | 0.01 | 0.10 | ||
| V$HFH4_01 | 0.01 | 0.31 | 8 | 0.1 | 0.2 | 2.7 | 0.01 | 0.08 | ||
| V$RORA1_01 | 2.E-04 | 0.03 | 16 | 0.3 | 0.2 | 2.5 | 1.E-03 | 4.E-03 | ||
| V$RORA2_01 | 1.E-03 | 0.11 | 6 | 0.1 | 0.4 | 4.4 | 0.03 | 0.14 | ||
| ChIP | HNF1-alpha | 0.04 | 0.11 | 6 | 0.1 | 0.2 | 2.3 | 0.15 | 0.25 | |
| Circ. | SCN circadian genes [17] | 0.05 | - | 13 | 0.1 | 0.3 | 1.6 | 0.07 | - | |
| EGF without interaction | GO | Protein binding | 0.02 | 0.06 | 7 | 0.3 | 0.1 | 2.5 | 0.01 | 0.06 |
| Protein kinase activity | 2.E-03 | 0.02 | 6 | 0.3 | 0.1 | 4.2 | 0.03 | 0.37 | ||
| Protein serine/threonine kinase activity | 1.E-03 | 0.02 | 6 | 0.3 | 0.1 | 4.8 | 0.02 | 0.32 | ||
| Transferase activity | 2.E-03 | 0.02 | 9 | 0.4 | 0.1 | 2.8 | 0.04 | 0.22 | ||
| CONS | V$CEBPGAMMA_Q6 | 0.02 | 1 | 11 | 0.4 | 0.1 | 1.9 | 0.01 | 0.08 | |
| V$TFIIA_Q6 | 0.02 | 1 | 12 | 0.4 | 0.1 | 1.8 | 0.03 | 0.04 | ||
| EGF: day+night | CONS | V$CREB_Q2 | 2.E-03 | 0.15 | 5 | 0.4 | 0.1 | 4.8 | 0.01 | 0.65 |
| V$CREB_Q4 | 9.E-04 | 0.12 | 6 | 0.5 | 0.1 | 4.5 | 4.E-03 | 0.55 | ||
| V$CREB_Q4_01 | 4.E-03 | 0.19 | 7 | 0.5 | 0.05 | 2.9 | 0.01 | 0.50 | ||
| ChIP | CREB (relaxed) | 0.11 | 0.11 | 6 | 0.5 | 0.03 | 1.7 | 0.24 | 0.35 | |
| EGF: night only | CONS | V$AP1_C | 3.E-03 | 0.14 | 27 | 0.7 | 0.1 | 1.5 | 0.03 | 0.17 |
| V$CEBP_Q2 | 6.E-04 | 0.13 | 20 | 0.5 | 0.1 | 2.0 | 0.01 | 0.08 | ||
| V$CEBP_Q2_01 | 0.02 | 0.40 | 31 | 0.8 | 0.1 | 1.3 | 0.04 | 0.16 | ||
| V$CEBP_Q3 | 5.E-03 | 0.16 | 34 | 0.8 | 0.1 | 1.3 | 0.01 | 0.09 | ||
| V$CREBP1_01 | 0.01 | 0.31 | 8 | 0.2 | 0.1 | 2.5 | 0.03 | 0.04 | ||
| V$ER_Q6_02 | 4.E-03 | 0.16 | 23 | 0.6 | 0.1 | 1.6 | 0.02 | 0.15 | ||
| V$HFH4_01 | 2.E-03 | 0.13 | 7 | 0.2 | 0.2 | 3.6 | 4.E-03 | 0.20 | ||
| V$LMO2COM_02 | 0.02 | 0.43 | 29 | 0.7 | 0.1 | 1.3 | 0.06 | 0.13 | ||
| V$RORA1_01 | 2.E-03 | 0.13 | 11 | 0.3 | 0.1 | 2.6 | 0.01 | 0.01 | ||
| V$RORA2_01 | 1.E-03 | 0.13 | 5 | 0.1 | 0.3 | 5.5 | 0.02 | 0.08 |
Statistically significant enrichments for specific cellular functions or TF binding sites (Attribute) are given for gene groups with specific circadian time dependent EGF responses (Gene group). Distinct gene groups are enriched for distinct and overlapping functions and TF binding sites. GO, gene ontology functional annotation; PAINT, TF binding sites predictions using PAINT [21]; CONS, TF binding sites based on evolutionary conservation [27]; ChIP, TF binding predictions based on the protein-DNA interaction data [28, 29]; Circ., established circadian rhythmic SCN gene expression [17]; pENRICH, gene group enrichment p value; pENRICH(FDR), false discovery rate (FDR) adjusted pENRICH; No. of genes, number of genes in gene group with the attribute; GFRAC, fraction of genes in the gene group with the attribute; AFRAC, fraction of all genes on the microarray with the attribute that are in the gene group; ENRICH, fold enrichment of the attribute in the gene group over random; pM(LOCAL), local meta-analysis enrichment p value; pM(GLOBAL), global meta-analysis enrichment p value. pENRICH, pENRICH(FDR), No. of genes, GFRAC, AFRAC, and ENRICH values are for results obtained using the standard normalization and are based on gene groups defined at a significance threshold of 1% FDR for GO enrichments, a significance threshold of 2% for PAINT, CONS and ChIP enrichments, and a significance threshold of 5% for circadian gene enrichments. pM(LOCAL) values are for standard normalization results and gene group significance thresholds of 5%, 2%, and 1% FDR for GO, PAINT, CONS, and ChIP enrichments and gene group significance thresholds of 20%, 10%, and 5% FDR for Circ. enrichments. Emphasized attributes are robust as indicated by both meta-analysis p values (pM(LOCAL) < 0.06 and pM(GLOBAL) < 0.1).