Polycomb inhibits histone acetylation by CBP by binding directly to its catalytic domain

Proceedings of the National Academy of Sciences of the United States of America
Feng TiePeter J Harte

Abstract

Drosophila Polycomb (PC), a subunit of Polycomb repressive complex 1 (PRC1), is well known for its role in maintaining repression of the homeotic genes and many others and for its binding to trimethylated histone H3 on Lys 27 (H3K27me3) via its chromodomain. Here, we identify a novel activity of PC: inhibition of the histone acetylation activity of CREB-binding protein (CBP). We show that PC and its mammalian CBX orthologs interact directly with the histone acetyltransferase (HAT) domain of CBP, binding to the previously identified autoregulatory loop, whose autoacetylation greatly enhances HAT activity. We identify a conserved PC motif adjacent to the chromodomain required for CBP binding and show that PC binding inhibits acetylation of histone H3. CBP autoacetylation impairs PC binding in vitro, and PC is preferentially associated with unacetylated CBP in vivo. PC knockdown elevates the acetylated H3K27 (H3K27ac) level globally and at promoter regions of some genes that are bound by both PC and CBP. Conversely, PC overexpression decreases the H3K27ac level in vivo and also suppresses CBP-dependent Polycomb phenotypes caused by overexpression of Trithorax, an antagonist of Polycomb silencing. We find that PC is physically asso...Continue Reading

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Citations

Feb 23, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Vincent LoubiereGiacomo Cavalli
Sep 22, 2017·Annual Review of Genetics·Leonie Ringrose
Sep 25, 2019·Epigenetics & Chromatin·Zain UmerMuhammad Tariq
Dec 7, 2017·Frontiers in Molecular Neuroscience·Felix L StruebingEldon E Geisert
Aug 7, 2017·Science Advances·Michelle PhersonDale Dorsett

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