Recent studies have shown that repressive chromatin machinery, including DNA methyltransferases and polycomb repressor complexes, binds to chromosomes throughout mitosis and their depletion results in increased chromosome size. In the present study, we show that enzymes that catalyze H3K9 methylation, such as Suv39h1, Suv39h2, G9a and Glp, are also retained on mitotic chromosomes. Surprisingly, however, mutants lacking histone 3 lysine 9 trimethylation (H3K9me3) have unusually small and compact mitotic chromosomes associated with increased histone H3 phospho Ser10 (H3S10ph) and H3K27me3 levels. Chromosome size and centromere compaction in these mutants were rescued by providing exogenous first protein lysine methyltransferase Suv39h1 or inhibiting Ezh2 activity. Quantitative proteomic comparisons of native mitotic chromosomes isolated from wild-type versus Suv39h1/Suv39h2 double-null mouse embryonic stem cells revealed that H3K9me3 was essential for the efficient retention of bookmarking factors such as Esrrb. These results highlight an unexpected role for repressive heterochromatin domains in preserving transcription factor binding through mitosis and underscore the importance of H3K9me3 for sustaining chromosome architecture and epigenetic memory during cell division.

最近的研究表明，抑制性染色质机制，包括 DNA 甲基转移酶和多梳抑制复合物，在整个有丝分裂过程中与染色体结合，它们的耗尽导致染色体大小增加。在本研究中，我们发现催化 H3K9 甲基化的酶，如 Suv39h1、Suv39h2、G9a 和 Glp，也保留在有丝分裂染色体上。然而，令人惊讶的是，缺乏组蛋白 3 赖氨酸 9 三甲基化 (H3K9me3) 的突变体具有异常小且紧凑的有丝分裂染色体，与组蛋白 H3 磷酸化 Ser10 (H3S10ph) 和 H3K27me3 水平增加相关。通过提供外源第一蛋白赖氨酸甲基转移酶 Suv39h1 或抑制 Ezh2 活性，可以挽救这些突变体中的染色体大小和着丝粒压缩。从野生型与 Suv39h1/Suv39h2 双无效小鼠胚胎干细胞分离的天然有丝分裂染色体的定量蛋白质组学比较表明，H3K9me3 对于有效保留书签因子（如 Esrrb）至关重要。这些结果突出了抑制性异染色质结构域在通过有丝分裂保持转录因子结合方面的意外作用，并强调了 H3K9me3 在细胞分裂过程中维持染色体结构和表观遗传记忆的重要性。