麻省理工学院Leonid A. Mirny研究组的一项最新研究，发现了异染色质驱动倒置核和常规核的区室化 。该项研究成果发表在2019年6月20日出版的《自然》上。

课题组结合Hi-C分析并结合显微镜和多聚体模拟。他们发现，发现异染色质区域间的吸引对建立区室化及着丝粒周边异染色质，可调节性异染色质和常染色质的建立至关重要。当加入异染色质和板层之间的相互作用时，相同的模型再现了传统的核组织。此外，研究模型允许其排除包含强常染色质相互作用的分区机制。综上所述，研究实验和模型表明，异染色质之间的相互吸引对于倒置和常规细胞核中活跃和不活跃基因组的相位分离是必不可少的，而染色质与薄层的相互作用对于从这些分离的阶段构建常规结构是必要的。

哺乳动物细胞的细胞核表现出基因组中活跃的全色区和不活跃的异色区在空间上的明显分离。在常规细胞核中，显微镜显示常染色质定位于核内，异染色质定位于核外。全基因组染色体构象捕获(Hi-C)分析表明，这种分离是常染色质和异染色质间的接触富集的格子状模式，并在它们之间耗尽。已经提出了许多形成小室的机制，如异染色质对核膜的吸引、相似染色质相互间的优先吸引、活性染色质中较高水平的染色质迁移率以及与转录相关的常染色质聚类。然而，由于传统核仁中染色质内和染色质层间相互作用难以解开，这些假说仍然没有定论。在夜间活动的哺乳动物中，倒转的杆状核内的间期染色体的显著重组为阐明空间分隔的机制提供了一个机会。

附：英文原文

Title: Heterochromatin drives compartmentalization of inverted and conventional nuclei

Author: Martin Falk, Yana Feodorova, Natalia Naumova, Maxim Imakaev, Bryan R. Lajoie, Heinrich Leonhardt, Boris Joffe, Job Dekker, Geoffrey Fudenberg, Irina Solovei, Leonid A. Mirny

Issue&Volume: Volume 570 Issue 7761, 20 June 2019

Abstract: The nucleus of mammalian cells displays a distinct spatial segregation of active euchromatic and inactive heterochromatic regions of the genome. In conventional nuclei, microscopy shows that euchromatin is localized in the nuclear interior and heterochromatin at the nuclear periphery. Genome-wide chromosome conformation capture (Hi-C) analyses show this segregation as a plaid pattern of contact enrichment within euchromatin and heterochromatin compartments3, and depletion between them. Many mechanisms for the formation of compartments have been proposed, such as attraction of heterochromatin to the nuclear lamina, preferential attraction of similar chromatin to each other higher levels of chromatin mobility in active chromatin and transcription-related clustering of euchromatin. However, these hypotheses have remained inconclusive, owing to the difficulty of disentangling intra-chromatin and chromatinlamina interactions in conventional nuclei18. The marked reorganization of interphase chromosomes in the inverted nuclei of rods in nocturnal mammals provides an opportunity to elucidate the mechanisms that underlie spatial compartmentalization. Here we combine Hi-C analysis of inverted rod nuclei with microscopy and polymer simulations. We find that attractions between heterochromatic regions are crucial for establishing both compartmentalization and the concentric shells of pericentromeric heterochromatin, facultative heterochromatin and euchromatin in the inverted nucleus. When interactions between heterochromatin and the lamina are added, the same model recreates the conventional nuclear organization. In addition, our models allow us to rule out mechanisms of compartmentalization that involve strong euchromatin interactions. Together, our experiments and modelling suggest that attractions between heterochromatic regions are essential for the phase separation of the active and inactive genome in inverted and conventional nuclei, whereas interactions of the chromatin with the lamina are necessary to build the conventional architecture from these segregated phases.

DOI: 10.1038/s41586-019-1275-3

Source:https://www.nature.com/articles/s41586-019-1275-3