Lamin C is required to establish genome organization after mitosis.
Lamin C is required to establish genome organization after mitosis.
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DOI：
10.1186/s13059-021-02516-7
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发表时间：
2021-11-15
期刊：
影响因子：
12.3
通讯作者：
Reddy KL
中科院分区：
文献类型：
--
作者：
Wong X;Hoskins VE;Melendez-Perez AJ;Harr JC;Gordon M;Reddy KL
基因组的动态3D组织是基因调控和发育的核心。核纤层通过将纤层相关结构域（LAD）束缚到核外围来影响基因组的组织。有证据表明，核纤层蛋白A和C是主要的核纤层蛋白参与外周协会的前降支，可能服务于不同的角色。在这里，我们研究染色体结构在小鼠细胞中，核纤层蛋白A或核纤层蛋白C下调。我们发现，核纤层蛋白C，而不是核纤层蛋白A，是所需的三维组织的LAD和整体染色体组织。当细胞退出有丝分裂并持续到早期G1时，定位存在显著差异，并与差异磷酸化有关。而核纤层蛋白A协会与新生的核膜（NE）在末期，核纤层蛋白C仍然在内部，周围的球状LAD聚集体上的常染色质区丰富。核纤层蛋白C与NE的关联被延迟到G1期几个小时，并且在时间和空间上与LAD的有丝分裂后NE关联相关。有丝分裂后LAD与NE的关联以及全局3D基因组组织仅在缺乏核纤层蛋白C而非核纤层蛋白A的细胞中受到干扰。核纤层蛋白C在退出有丝分裂期间调节LAD动力学，并且是哺乳动物细胞中基因组组织的关键调节因子。这揭示了核纤层蛋白C在基因组组织中的意想不到的核心作用，包括染色体间LAD-LAD分离和NE处的LAD支架，提出了关于核纤层蛋白A/C在细胞功能和疾病中的个体和重叠作用的有趣问题。在线版本包含补充材料，可通过10.1186/s13059-021-02516-7获得。
The dynamic 3D organization of the genome is central to gene regulation and development. The nuclear lamina influences genome organization through the tethering of lamina-associated domains (LADs) to the nuclear periphery. Evidence suggests that lamins A and C are the predominant lamins involved in the peripheral association of LADs, potentially serving different roles. Here, we examine chromosome architecture in mouse cells in which lamin A or lamin C are downregulated. We find that lamin C, and not lamin A, is required for the 3D organization of LADs and overall chromosome organization. Striking differences in localization are present as cells exit mitosis and persist through early G1 and are linked to differential phosphorylation. Whereas lamin A associates with the nascent nuclear envelope (NE) during telophase, lamin C remains in the interior, surrounding globular LAD aggregates enriched on euchromatic regions. Lamin C association with the NE is delayed until several hours into G1 and correlates temporally and spatially with the post-mitotic NE association of LADs. Post-mitotic LAD association with the NE, and global 3D genome organization, is perturbed only in cells depleted of lamin C, and not lamin A. Lamin C regulates LAD dynamics during exit from mitosis and is a key regulator of genome organization in mammalian cells. This reveals an unexpectedly central role for lamin C in genome organization, including inter-chromosomal LAD-LAD segregation and LAD scaffolding at the NE, raising intriguing questions about the individual and overlapping roles of lamin A/C in cellular function and disease. The online version contains supplementary material available at 10.1186/s13059-021-02516-7.
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影响因子：
64.5
作者：
Kind J;Pagie L;de Vries SS;Nahidiazar L;Dey SS;Bienko M;Zhan Y;Lajoie B;de Graaf CA;Amendola M;Fudenberg G;Imakaev M;Mirny LA;Jalink K;Dekker J;van Oudenaarden A;van Steensel B
通讯作者：
van Steensel B
DOI：
10.1083/jcb.123.6.1671
发表时间：
1993-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Belmont AS;Zhai Y;Thilenius A
通讯作者：
Thilenius A
DOI：
10.1073/pnas.1111780109
发表时间：
2012-02-14
影响因子：
11.1
作者：
Jung, Hea-Jin;Coffinier, Catherine;Fong, Loren G.
通讯作者：
Fong, Loren G.
影响因子：
64.8
作者：
Guelen, Lars;Pagie, Ludo;van Steensel, Bas
通讯作者：
van Steensel, Bas
影响因子：
64.8
作者：
Larson AG;Elnatan D;Keenen MM;Trnka MJ;Johnston JB;Burlingame AL;Agard DA;Redding S;Narlikar GJ
通讯作者：
Narlikar GJ