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SUMO ylated PRC 1 controls histone H3.3 deposition and genome integrity of embryonic heterochromatin
Author(s) -
Liu Zichuan,
Tardat Mathieu,
Gill Mark E,
Royo Helene,
Thierry Raphael,
Ozonov Evgeniy A,
Peters Antoine HFM
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019103697
Subject(s) - biology , heterochromatin , histone , microbiology and biotechnology , embryonic stem cell , histone h3 , heterochromatin protein 1 , genetics , genome , chromatin , gene
Chromatin integrity is essential for cellular homeostasis. Polycomb group proteins modulate chromatin states and transcriptionally repress developmental genes to maintain cell identity. They also repress repetitive sequences such as major satellites and constitute an alternative state of pericentromeric constitutive heterochromatin at paternal chromosomes (pat‐ PCH ) in mouse pre‐implantation embryos. Remarkably, pat‐ PCH contains the histone H3.3 variant, which is absent from canonical PCH at maternal chromosomes, which is marked by histone H3 lysine 9 trimethylation (H3K9me3), HP 1, and ATRX proteins. Here, we show that SUMO 2‐modified CBX 2‐containing Polycomb Repressive Complex 1 ( PRC 1) recruits the H3.3‐specific chaperone DAXX to pat‐ PCH , enabling H3.3 incorporation at these loci. Deficiency of Daxx or PRC 1 components Ring1 and Rnf2 abrogates H3.3 incorporation, induces chromatin decompaction and breakage at PCH of exclusively paternal chromosomes, and causes their mis‐segregation. Complementation assays show that DAXX ‐mediated H3.3 deposition is required for chromosome stability in early embryos. DAXX also regulates repression of PRC 1 target genes during oogenesis and early embryogenesis. The study identifies a novel critical role for Polycomb in ensuring heterochromatin integrity and chromosome stability in mouse early development.