SUMOylated PRC1 controls histone H3.3 deposition and genome integrity of embryonic heterochromatin.

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), 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, enabling H3.3 incorporation at these loci. Deficiency of Daxx or PRC1 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 PRC1 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. Synopsis: Formation of pericentromeric heterochromatin (PCH) in early mouse embryos involves selective incorporation of the histone variant H3.3. Polycomb repressive complex 1 (PRC1) facilitates this by recruitment of H3.3 chaperone/remodeler DAXX‐ATRX in a SUMOylation‐dependent manner. Histone chaperone DAXX controls H3.3 deposition into pericentromeric heterochromatin exclusively at paternal chromosomes of early mouse embryos.Canonical PRC1, but not PRC2, is required for recruitment of DAXX and H3.3 deposition at paternal PCH.SUMOylation of the PRC1 component CBX2 mediates interaction between CBX2 and DAXX.DAXX contributes to PRC1‐dependent gene repression in oocytes. [ABSTRACT FROM AUTHOR]