Figure 3.

Transcriptional regulatory relationships between DE-mTFs and their target genes. (a) Overlaps of groups 1–12 with pluripotency-related genes in mESCs. Groups 1 and 3 significantly (P<0.01) overlapped with 844 pluripotency-related genes, whereas groups 7 and 9 significantly (P<0.01) overlapped with 1178 differentiation-related genes. The red line denotes the cutoff P-value. (b) DE-mTFs that significantly (FDR<0.05) regulate the genes in groups 1 and 3. The pie chart shows which groups of DEGs included the five and 14 DE-mTFs for groups 1 and 3, respectively. (c) The significance of the GOBPs that are regulated by the 52 DE-mTFs in groups 1–12. The significance for each pair of DE-mTF and GOBP was estimated as the enrichment P-value (x-axis) obtained from the DAVID software for 158 and 780 target genes in groups 1 and 3, respectively. The default P-value cutoff in DAVID is denoted as red dotted lines. The red boxes at the center indicate GOBPs significantly enriched by all the genes in groups 1 (BP-G1) and 3 (BP-G3). (d) The significance of the GOBPs that are regulated by the five and 14 DE-mTFs for groups 1 (left) and 3 (right), respectively. The significance for each pair of DE-mTF and GOBP was computed as the fraction of the genes regulated by the DE-mTF among all the genes DEGs involved in the GOBP. The color gradient shows the relative proportions of such genes. The red boxes at the center indicate representative GOBPs in groups 1 (BP-G1) and 3 (BP-G3). The tables show the association of the DE-mTFs with cell proliferation-related processes (red for group 1 and orange for group 3), stem cell maintenance (blue) and epigenetic regulation (green). (e) PCR analysis of the differential expression of four representative DE-mTFs and their representative target genes involved in stem cell maintenance and epigenetic regulation as well as three representative DE-mTFs (Zfp143, Trp53 and E2f4) and their representative target genes involved in cell proliferation-related processes