Figure 7. Summary schematic of KLF4 promoter methylation mechanisms contributing to suppression of transcription.
DF-induced DNMT3A enrichment of endothelial KLF4 promoter near the TSS increased CpG methylation. Hypermethylation prevented MEF2-complex binding resulting in inhibition of KLF4 transcription. Decreased KLF4 expression can lower the interaction of KLF4 with its transcription targets independently of their methylation status leading to a pro-inflammatory, pro-atherosclerosis phenotype. Intervention by DNMT inhibitors (RG108; 5-Aza) can rescue this pathway.