FIGURE 6.

Schematic diagram of the proposed model. Shown is the model for β-catenin-mediated and PPAR-δ-activated vascular endothelial growth factor A (VEGFA) transcription. The chromatin loop is formed by β-catenin near the VEGFA gene in HCT116 cells grown in basal serum-free condition. β-Catenin occupies the far upstream TBE1 and TBE3 along with TCF-4 at upstream TBE sites and NF-κB p65 at downstream sites. At this basal state VEGFA transcription is repressed. Upon activation by GW501516, the chromatin loop is released by dissociation of β-catenin in TBE1 and association of PPAR-δ in upstream TBEs. VEGFA transcription is derepressed or activated by such remodeling of transcription factors near the gene that accompanied by the release of chromatin loop. Therefore, β-catenin-mediated chromatin loops near the VEGFA gene are prerequisite for PPAR-δ-activated VEGFA transcription in colorectal carcinoma, such as HCT116 cells.