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.

中文翻译：

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SUMOylated PRC1控制组蛋白H3.3沉积和胚胎异染色质的基因组完整性。

染色质完整性对于细胞稳态至关重要。聚梳组蛋白调节染色质状态并转录抑制发育基因以维持细胞身份。它们还抑制重复序列（例如主要卫星），并在小鼠植入前胚胎的父系染色体（pat-PCH）处构成着眼点中心组成型异染色质的替代状态。值得注意的是，pat-PCH包含组蛋白H3.3变体，这是母体染色体上规范PCH所不存在的，其特征在于组蛋白H3赖氨酸9三甲基化（H3K9me3），HP 1和ATRX蛋白。在这里，我们显示了SUMO 2修饰的含CBX 2的Polycomb Repressive Complex 1（PRC 1）募集了H3.3特异性伴侣蛋白DAXX到pat-PCH中，使H3.3可以在这些基因座上掺入。Daxx的不足或PRC 1成分Ring1和Rnf2废除H3.3掺入，在仅父本染色体的PCH上引起染色质分解和断裂，并导致它们的错误分离。互补分析表明，DAXX介导的H3.3沉积对于早期胚胎的染色体稳定性是必需的。DAXX还调节卵母细胞发生和早期胚胎发生过程中PRC 1目标基因的抑制。该研究确定了Polycomb在确保小鼠早期发育中异染色质完整性和染色体稳定性方面的新型关键作用。