Heterochromatin enriched in histone H3 lysine 9 methylation (H3K9me) and HP1 proteins coats chromosomal domains throughout the eukaryotic genome to regulate gene expression and maintain genome stability. How heterochromatin assembly mechanisms are... The fission yeast Schizosaccharomyces pombe is a powerful genetic model system for uncovering fundamental principles of heterochromatin assembly and epigenetic inheritance of chromatin states. Heterochromatin defined by histone H3 lysine 9 methylation and HP1 proteins coats large chromosomal domains at centromeres, telomeres, and the mating-type (mat) locus. Although genetic and biochemical studies have provided valuable insights into heterochromatin assembly, many key mechanistic details remain unclear. Here, we use a sensitized reporter system at the mat locus to screen for factors affecting heterochromatic silencing. In addition to known components of heterochromatin assembly pathways, our screen identified eight new factors including the cohesin-associated protein Pds5. We find that Pds5 enriched throughout heterochromatin domains is required for proper maintenance of heterochromatin. This function of Pds5 requires its associated Eso1 acetyltransferase, which is implicated in the acetylation of cohesin. Indeed, introducing an acetylation-mimicking mutation in a cohesin subunit suppresses defects in heterochromatin assembly in pds5∆ and eso1∆ cells. Our results show that in cells lacking Pds5, cohesin interferes with heterochromatin assembly. Supporting this, eliminating cohesin from the mat locus in the pds5∆ mutant restores both heterochromatin assembly and gene silencing. These analyses highlight an unexpected requirement for Pds5 in ensuring proper coordination between cohesin and heterochromatin factors to effectively maintain gene silencing.

中文翻译：

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粘连蛋白阻碍缺乏 Pds5 的裂殖酵母细胞中的异染色质组装。

富含组蛋白 H3 赖氨酸 9 甲基化 (H3K9me) 和 HP1 蛋白的异染色质覆盖整个真核基因组的染色体结构域，以调节基因表达并维持基因组稳定性。异染色质组装机制是如何...裂殖酵母裂殖酵母是一个强大的遗传模型系统，用于揭示异染色质组装和染色质状态的表观遗传的基本原理。由组蛋白 H3 赖氨酸 9 甲基化和 HP1 蛋白定义的异染色质覆盖着丝粒、端粒和交配型 (mat) 基因座的大染色体结构域。尽管遗传和生化研究为异染色质组装提供了有价值的见解，但许多关键机制细节仍不清楚。在这里，我们在垫位点使用敏化报告系统来筛选影响异染色质沉默的因素。除了异染色质组装途径的已知成分之外，我们的筛选还确定了八个新因子，包括粘连蛋白相关蛋白 Pds5。我们发现，Pds5 在整个异染色质域中富集是正确维持异染色质所必需的。Pds5 的这一功能需要其相关的 Eso1 乙酰转移酶，该酶参与粘连蛋白的乙酰化。事实上，在粘连蛋白亚基中引入乙酰化模拟突变可以抑制 pds5Δ 和 eso1Δ 细胞中异染色质组装的缺陷。我们的结果表明，在缺乏 Pds5 的细胞中，粘连蛋白会干扰异染色质组装。支持这一点的是，从 pds5Δ 突变体的 mat 基因座中消除粘连蛋白可以恢复异染色质组装和基因沉默。这些分析强调了 Pds5 在确保粘连蛋白和异染色质因子之间的适当协调以有效维持基因沉默方面的意外要求。