Figure 7.

Communication between distal intergenic RNAPII and FOXO3 bound regions and adjacent target gene expression. (A) Status of the adjacent gene is predictive for RNAPII increase at intergenic FOXO3 bound regions. The status of the closest gene for every FOXO3 bound intergenic RNAPII peak was determined for all peaks within 5–100 kb to the TSS of the closest gene. Fold change in RNAPII occupancy (DLD1-F3 cells, 4 h versus untreated) for peaks with unchanged and upregulated adjacent gene are shown (category numbers indicated, median within box, P-value from Mann–Whitney–Wilcoxon test). (B) 4C signal and RNAPII and FOXO3 occupancy surrounding the KLF5 locus. An 18-kb upstream FOXO3 and RNAPII occupied putative enhancer was used as viewpoint (eye) for 4C analysis. Stars denote increased signal in other FOXO3 bound RNAPII occupied intergenic regions. (C) Model for FOXO3-induced target gene expression. Enhancers are marked by the presence of H3K4me1 and FOXO3 binding is accompanied by an increase of H3K27Ac and recruitment of RNAPII. Cell type specificity of enhancers and chromatin architecture could explain context dependency in gene activation. A model is shown in which pre-existing enhancers and promoter–enhancer loops are responsible for differential responses to FOXO activity; gene A is FOXO responsive in cell type I, while gene B is responsive only in cell type II.