Lamin C is required to establish genome organization after mitosis

Abstract Background 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...

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Autores principales:	Xianrong Wong, Victoria E. Hoskins, Ashley J. Melendez-Perez, Jennifer C. Harr, Molly Gordon, Karen L. Reddy
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Biology (General) QH301-705.5 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/c3c02a39c176426f994be672983a5aeb
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spelling	oai:doaj.org-article:c3c02a39c176426f994be672983a5aeb2021-11-21T12:41:55ZLamin C is required to establish genome organization after mitosis10.1186/s13059-021-02516-71474-760Xhttps://doaj.org/article/c3c02a39c176426f994be672983a5aeb2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13059-021-02516-7https://doaj.org/toc/1474-760XAbstract Background 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. Results 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. Conclusions 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.Xianrong WongVictoria E. HoskinsAshley J. Melendez-PerezJennifer C. HarrMolly GordonKaren L. ReddyBMCarticleBiology (General)QH301-705.5GeneticsQH426-470ENGenome Biology, Vol 22, Iss 1, Pp 1-27 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5 Genetics QH426-470
spellingShingle	Biology (General) QH301-705.5 Genetics QH426-470 Xianrong Wong Victoria E. Hoskins Ashley J. Melendez-Perez Jennifer C. Harr Molly Gordon Karen L. Reddy Lamin C is required to establish genome organization after mitosis
description	Abstract Background 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. Results 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. Conclusions 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.
format	article
author	Xianrong Wong Victoria E. Hoskins Ashley J. Melendez-Perez Jennifer C. Harr Molly Gordon Karen L. Reddy
author_facet	Xianrong Wong Victoria E. Hoskins Ashley J. Melendez-Perez Jennifer C. Harr Molly Gordon Karen L. Reddy
author_sort	Xianrong Wong
title	Lamin C is required to establish genome organization after mitosis
title_short	Lamin C is required to establish genome organization after mitosis
title_full	Lamin C is required to establish genome organization after mitosis
title_fullStr	Lamin C is required to establish genome organization after mitosis
title_full_unstemmed	Lamin C is required to establish genome organization after mitosis
title_sort	lamin c is required to establish genome organization after mitosis
publisher	BMC
publishDate	2021
url	https://doaj.org/article/c3c02a39c176426f994be672983a5aeb
work_keys_str_mv	AT xianrongwong lamincisrequiredtoestablishgenomeorganizationaftermitosis AT victoriaehoskins lamincisrequiredtoestablishgenomeorganizationaftermitosis AT ashleyjmelendezperez lamincisrequiredtoestablishgenomeorganizationaftermitosis AT jennifercharr lamincisrequiredtoestablishgenomeorganizationaftermitosis AT mollygordon lamincisrequiredtoestablishgenomeorganizationaftermitosis AT karenlreddy lamincisrequiredtoestablishgenomeorganizationaftermitosis
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Lamin C is required to establish genome organization after mitosis

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