condensin 介导的有丝分裂折叠在间期染色质中留下结构印记
Condensins-mediated mitotic folding persists as a structural echo in interphase chromatin
研究利用携带生长素诱导降解标签的 SMC 复合物亚基小鼠胚胎干细胞系,通过 Hi-C 数据厘清了 condensin 在间期细胞核内塑造染色质接触中的作用。结果显示,敲低 condensin I 会削弱染色质向 A、B 区室的分离;condensin 在有丝分裂期建立的接触模式在间期得以保留,提示有丝分裂染色体折叠存在结构记忆。condensin 还影响染色中心组织:有丝分裂期缺失 condensin II 时,着丝粒趋于聚集,形成近着丝粒异染色质超簇;而敲低 condensin I 则减少异染色质簇数量,与染色体领地性增强一致。
来源:Nucleic Acids Research · doi.org
The structural maintenance of chromosomes (SMC) protein complexes, cohesin and condensins, orchestrate cell cycle-dependent transitions in chromosome folding: from the relatively decondensed interphase chromatin, organized into dynamic DNA loops by cohesin, to the highly condensed arrays of DNA loops in mitotic chromosomes formed by condensins. Here, using Hi-C data from mouse embryonic stem cell lines with auxin-inducible degron-tagged subunits of SMC complexes, we clarify the role of condensins in shaping chromatin contacts within the interphase nucleus. We found that depletion of condensin I leads to weakened segregation of chromatin into A and B compartments. We also show that the contact patterns established by condensins during mitosis are preserved in interphase, suggesting a structural memory of mitotic chromosome folding. Condensins influence chromocenter organization: in the absence of condensin II during mitosis, centromeres tend to cluster, forming hyperclusters of pericentric heterochromatin. In contrast, depletion of condensin I reduces the number of heterochromatin clusters, consistent with enhanced chromosome territoriality. By combining a cohesin-degron system with Mcph1 knockout, we established an artificial model in which condensin II becomes the major driver of chromatin folding in interphase nuclei following cohesin depletion. Unlike extrusive cohesin, condensin II does not stall at sequence-specific sites and forms large, randomly positioned loops on interphase chromatin. Moreover, condensin II activity during interphase does not interfere with cohesin-dependent structures such as TADs and chromatin loops.