Two competing mechanisms of DNMT3A recruitment regulate the dynamics of de novo DNA methylation at PRC1-targeted CpG islands.

ABSTRACT: Precise deposition of CpG methylation is critical for mammalian development and tissue homeostasis and is often dysregulated in human diseases. The localization of de novo DNA methyltransferase DNMT3A is facilitated by its PWWP domain recognizing histone H3 lysine 36 (H3K36) methylation^1,2 and is normally depleted at CpG islands (CGIs)³. However, methylation of CGIs regulated by Polycomb repressive complexes (PRCs) has also been observed^4-8. Here, we report that DNMT3A PWWP domain mutations identified in paragangliomas⁹ and microcephalic dwarfism¹⁰ promote aberrant localization of DNMT3A to CGIs in a PRC1-dependent manner. DNMT3A PWWP mutants accumulate at regions containing PRC1-mediated formation of monoubiquitylated histone H2A lysi

SUBMITTER: Weinberg DN 

PROVIDER: S-EPMC8283687 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature