Figure 8

A hypothetical deregulatory hierarchy. (A) TFs with high affinity binding overrepresented in the promoters of genes in the functional clusters and in promoters of their mouse orthologs. Only binding predictions with FDR ≤ 0.05 are shown. (B) Nine deregulated genes with strong evidence of regulation by CREB. Column titles: Name, gene names; AvgD deregulation scores averaged over RelA, ATM and p53; YH, yeast homologs (NA - homolog not known); DB, p-values for deletion-buffering of the homologs by SKO1, a CREB homolog in yeast. YPD, p-values for the binding of SKO1 to the promotors of the yeast homologs in YPD medium; MMS, p-values for SKO1 binding to the promoters of the homologs in cells damaged by MMS. CREB, p-values for CREB binding to promoter, averaged over three time points of forskolin stimulation in HEK293T cells. Colored background marks genes from the DNA repair cluster that have a high affinity binding of CREB to their promoters conserved in mouse. (C) Putative gene deregulatory network. Top: ATM pathway. Middle: The pathway deregulating CREB. Below: CREB regulating its most likely gene targets (the genes shown in B). Genes are colored in shades of violet according to their deregulation, averaged over the regulators RelA, ATM and p53. The hierarchy is a hypothetical mechanistic explanation of deregulation of those genes, observed between the healthy and the damaged cells.