麻省大学陈医学院Job Dekker小组近日取得一项新成果。经过不懈努力，他们的最新研究探明了间期染色体构象由有丝分裂染色体或细胞质遗传的不同折叠程序指定。这一研究成果发表在2025年12月22日出版的国际学术期刊《自然—细胞生物学》上。

为了揭示间期折叠是如何遗传的，该课题组研究人员开发了一种方法，将染色体内在机制与G1核重组期间通过细胞质传播的机制分离开来。在有丝分裂退出过程中，对核胞质运输的建立所必需的蛋白质的诱导降解使折叠程序具有不同的遗传模式。

在这里，该团队表明基因组区隔化完全是由染色体内在因素驱动的。除了传统的区室分离外，染色体固有的折叠程序导致有丝分裂书签顺式调控元件在基因组尺度上的显著微区室化。微室构象在末期短暂形成，随后在G1早期通过细胞质遗传的第二个折叠程序进行调节。该程序包括内聚蛋白介导的环外旋和参与转录和RNA加工的因素。当细胞退出有丝分裂时，染色体固有折叠程序和细胞质遗传折叠程序的相互作用决定了间期染色质的构象。

研究人员表示，在每次细胞分裂时，身份特异性的染色体构象将被重新建立。

附：英文原文

Title: Interphase chromosome conformation is specified by distinct folding programmes inherited through mitotic chromosomes or the cytoplasm

Author: Schooley, Allana, Venev, Sergey V., Aksenova, Vasilisa, Lehman, Jesse W., Navarrete, Emily, Pai, Athma A., Dasso, Mary, Dekker, Job

Issue&Volume: 2025-12-22

Abstract: Identity-specific chromosome conformation must be re-established at each cell division. To uncover how interphase folding is inherited, we developed an approach that segregates chromosome-intrinsic mechanisms from those propagated through the cytoplasm during G1 nuclear reassembly. Inducible degradation of proteins essential for the establishment of nucleocytoplasmic transport during mitotic exit enabled analysis of folding programmes with distinct modes of inheritance. Here we show that genome compartmentalization is driven entirely by chromosome-intrinsic factors. In addition to conventional compartmental segregation, the chromosome-intrinsic folding programme leads to prominent genome-scale microcompartmentalization of mitotically bookmarked cis-regulatory elements. The microcompartment conformation forms transiently during telophase and is subsequently modulated by a second folding programme inherited through the cytoplasm in early G1. This programme includes cohesin-mediated loop extrusion and factors involved in transcription and RNA processing. The combined and interdependent action of chromosome-intrinsic and cytoplasmic inherited folding programmes determines the interphase chromatin conformation as cells exit mitosis.

DOI: 10.1038/s41556-025-01828-1

Source: https://www.nature.com/articles/s41556-025-01828-1