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SUMO ylated PRC 1 controls histone H3.3 deposition and genome integrity of embryonic heterochromatin

Liu, Zichuan and Tardat, Mathieu and Gill, Mark E and Royo, Helene and Thierry, Raphael and Ozonov, Evgeniy A and Peters, Antoine HFM (2020) SUMO ylated PRC 1 controls histone H3.3 deposition and genome integrity of embryonic heterochromatin. The EMBO Journal. pp. 1-24. ISSN 0261-4189

Abstract

Chromatin integrity is essential for cellular homeostasis. Polycombgroup proteins modulate chromatin states and transcriptionallyrepress developmental genes to maintain cell identity. They alsorepress repetitive sequences such as major satellites and consti-tute an alternative state of pericentromeric constitutive hete-rochromatin at paternal chromosomes (pat-PCH) in mouse pre-implantation embryos. Remarkably, pat-PCH contains the histoneH3.3 variant, which is absent from canonical PCH at maternal chro-mosomes, which is marked by histone H3 lysine 9 trimethylation(H3K9me3), HP1, and ATRX proteins. Here, we show that SUMO2-modified CBX2-containing Polycomb Repressive Complex 1 (PRC1)recruits the H3.3-specific chaperone DAXX to pat-PCH, enablingH3.3 incorporation at these loci. Deficiency of Daxx or PRC1 compo-nents Ring1 and Rnf2 abrogates H3.3 incorporation, induces chro-matin decompaction and breakage at PCH of exclusively paternalchromosomes, and causes their mis-segregation. Complementationassays show that DAXX-mediated H3.3 deposition is required forchromosome stability in early embryos. DAXX also regulates repres-sion of PRC1 target genes during oogenesis and early embryogene-sis. The study identifies a novel critical role for Polycomb inensuring heterochromatin integrity and chromosome stability inmouse early development.

Item Type: Article
Date Deposited: 24 Jun 2020 00:45
Last Modified: 24 Jun 2020 00:45
URI: https://oak.novartis.com/id/eprint/42946

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