STAG1和STAG2在有丝分裂后基因组重折叠中的不同和补偿性作用
Distinct and compensatory roles of STAG1 and STAG2 in post-mitotic genome refolding.
摘要(中文译文)
真核基因组的三维结构在很大程度上由包含STAG1或STAG2亚基的黏连蛋白（cohesin）复合物所塑造。然而，它们在分裂后基因组重新折叠中的作用仍不清楚。在此，我们确立STAG2为该过程的主要旁系同源蛋白和首要调控者。我们发现，在有丝分裂退出后，STAG1缺失对基因组重新折叠或转录再激活的影响微乎其微，而STAG2则以阶段和染色质环境依赖的方式调控基因组重塑。在G1早期，STAG2促进小的常染色质结构环、增强子-启动子接触和转录再启动；在G1晚期，它通过限制更具持续性的STAG1-黏连蛋白来抑制大环的形成。STAG2的持续性受CTCF路障而非基因组行进距离的限制。联合缺失会导致结构环的协同性丧失和更强烈的转录失调，但残余的染色质结合黏连蛋白仍保留可测量的挤出能力。总之，这些结果确立STAG2为分裂后时空染色质重组的主要调控者，而STAG1则为其稳健性提供补偿性支持。
Abstract
The 3D architecture of the eukaryotic genome is largely shaped by cohesin complexes containing either STAG1 or STAG2 subunits. Yet, their roles in post-mitotic genome refolding remain unclear. Here, we establish STAG2 as the predominant paralog and primary orchestrator of this process. We find that upon mitotic exit, STAG1 depletion imposes negligible effects on genome refolding or transcription reactivation, whereas STAG2 regulates genome remodeling in a stage- and chromatin-context-dependent manner. In early-G1, STAG2 promotes small euchromatic structural loops, enhancer-promoter contacts and transcriptional refiring; in late-G1, it suppresses large loops by limiting the more processive STAG1-cohesin. STAG2 processivity is constrained by CTCF roadblocks rather than genomic traveling distance. Co-depletion causes synergistic loss of structural loops and stronger transcriptional dysregulation, yet residual chromatin-bound cohesin retains measurable extrusion capacity. Together, these results establish STAG2 as the principal regulator of post-mitotic spatiotemporal chromatin reorganization, while STAG1 provides compensatory support for robustness.
如何引用
AMA
Manzhu Wang, Yabing Zhang, Fengnian Shan, Chongren Pei, Fuhai Liu, Sijian Xia, et al. Distinct and compensatory roles of STAG1 and STAG2 in post-mitotic genome refolding.. Nature communications. 2026; doi:10.1038/s41467-026-74870-8.
APA
Manzhu Wang, Yabing Zhang, Fengnian Shan, Chongren Pei, Fuhai Liu, Sijian Xia, et al (2026). Distinct and compensatory roles of STAG1 and STAG2 in post-mitotic genome refolding.. Nature communications. https://doi.org/10.1038/s41467-026-74870-8
GB/T 7714
Manzhu Wang, Yabing Zhang, Fengnian Shan, Chongren Pei, Fuhai Liu, Sijian Xia, et al. Distinct and compensatory roles of STAG1 and STAG2 in post-mitotic genome refolding.[J]. Nature communications, 2026 doi:10.1038/s41467-026-74870-8.
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