Structural basis for the inhibition of PRC2 by active transcription histone posttranslational modifications.

ABSTRACT: Polycomb repressive complex 2 (PRC2) is an epigenetic regulator essential for embryonic development and maintenance of cell identity that trimethylates histone H3 at lysine 27 (H3K27me3) leading to gene silencing. PRC2 is regulated by association with protein cofactors and crosstalk with histone posttranslational modifications. Trimethylated histone H3 K4 (H3K4me3) and K36 (H3K36me3) localize to sites of active transcription where H3K27me3 is absent and inhibit PRC2 activity through unknown mechanisms. Using cryo-electron microscopy we reveal that histone H3 tails modified with H3K36me3 engage poorly with the PRC2 active site and preclude its effective interaction with chromatin, while the H3K4me3 modification binds to the allosteric site in the EED subunit, acting as an antagonist that co

SUBMITTER: Cookis T 

PROVIDER: S-EPMC10871338 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature