Fig. 9
From: A DNMT3A PWWP mutation leads to methylation of bivalent chromatin and growth retardation in mice
Model of molecular mechanisms acting at bivalent domains. a Representation of current understanding of bivalent domain regulation. The PRC2 complex deposits H3K27me3 and compacts chromatin across the promoters and surrounding regions of transcriptionally silent, developmental genes62. TET proteins are recruited, which result in active removal of DNA methylation and protection of bivalent chromatin from de novo DNMTs71. DNMT3A is recruited to bivalent chromatin shores through an unknown mechanism, enabling active establishment of DNA methylation at the boundaries60,70,71. Through the competing actions of TETs and DNMT3A there is a cycle of DNA methylation turnover at the boundaries of bivalent domains. b Representation of bivalent chromatin dynamics in the presence of DNMT3AD329A. The mutant protein is able to access bivalent chromatin and establish methylation across the whole domain. The presence of DNA methylation appears to influence the local chromatin environment and results in reduction of H3K27me3, potentially due to exclusion of PRC2 from methylated DNA. As a consequence, some genes become de-repressed and show an increase in promoter H3K4me3, while others maintain their transcriptional silencing, this is likely dependent on the availability and strength of necessary transcription factors
