The polycomb group protein CBX2 is an important epigenetic reader involved in cell proliferation and differentiation. While CBX2 overexpression occurs in a wide range of human tumors, targeted deletion results in homeotic transformation, proliferative defects, and premature senescence. However, its cellular function(s) and whether it plays a role in maintenance of genome stability remain to be determined. Here, we demonstrate that loss of CBX2 in mouse fibroblasts induces abnormal large-scale chromatin structure and chromosome instability. Integrative transcriptome analysis and ATAC-seq revealed a significant dysregulation of transcripts involved in DNA repair, chromocenter formation, and tumorigenesis in addition to changes in chromatin accessibility of genes involved in lateral sclerosis, basal transcription factors, and folate metabolism. Notably, Cbx2−/− cells exhibit prominent decondensation of satellite DNA sequences at metaphase and increased sister chromatid recombination events leading to rampant chromosome instability. The presence of extensive centromere and telomere defects suggests a prominent role for CBX2 in heterochromatin homeostasis and the regulation of nuclear architecture.

中文翻译：

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CBX2 的缺失会导致基因组不稳定和衰老相关的染色体重排

多梳族蛋白 CBX2 是参与细胞增殖和分化的重要表观遗传读数器。虽然 CBX2 过度表达发生在多种人类肿瘤中，但靶向缺失会导致同源异型转化、增殖缺陷和过早衰老。然而，其细胞功能以及是否在维持基因组稳定性中发挥作用仍有待确定。在这里，我们证明小鼠成纤维细胞中 CBX2 的缺失会诱导异常的大规模染色质结构和染色体不稳定。综合转录组分析和 ATAC-seq 显示，除了涉及侧索硬化症、基础转录因子和叶酸代谢的基因的染色质可及性发生变化外，参与 DNA 修复、染色中心形成和肿瘤发生的转录物也存在显着失调。值得注意的是，Cbx2−/− 细胞在中期表现出卫星 DNA 序列的显着解缩，并且姐妹染色单体重组事件增加，导致染色体不稳定。广泛着丝粒和端粒缺陷的存在表明 CBX2 在异染色质稳态和核结构调节中发挥着重要作用。