PT  - JOURNAL ARTICLE
AU  - X Wong
AU  - VE Hoskins
AU  - JC Harr
AU  - M Gordon
AU  - KL Reddy
TI  - Lamin C regulates genome organization after mitosis
AID  - 10.1101/2020.07.28.213884
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.28.213884
4099  - http://biorxiv.org/content/early/2020/07/28/2020.07.28.213884.short
4100  - http://biorxiv.org/content/early/2020/07/28/2020.07.28.213884.full
AB  - The dynamic 3D organization of the genome is central to the regulation of gene expression and developmental progression, with its disruption being implicated in various diseases. The nuclear lamina, a proteinaceous meshwork underlying the nuclear envelope (NE), provides both structural and regulatory influences on genome organization through the tethering of large inactive genomic regions, called Lamina Associated Domains (LADs), to the nuclear periphery. Evidence suggests that the A type lamins, lamins A and C, are the predominant lamins involved in the peripheral association of LADs, with these two isotypes forming distinct networks and potentially involved in different cellular processes. Here we tested whether lamins A and C have distinct roles in genome organization by examining chromosome architecture in cells in which lamin C or lamin A are specifically down-regulated. We find that lamin C (not lamin A) is required for the 3D organization of LADs and overall chromosome organization in the cell nucleus. Striking differences in the localization of lamin A and lamin C are present as cells exit mitosis that persist through early G1. Whereas lamin A associates with the nascent NE during telophase, lamin C remains in the interior surrounding nucleoplasmic LAD clusters. 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 consequently global 3D genome organization, is perturbed only in cells depleted of lamin C, and not in cells depleted of lamin A. We conclude that lamin C regulates LAD dynamics after mitosis and is a key regulator of genome organization in mammalian cells. These findings reveal an unexpectedly central role for lamin C in genome organization, including both inter-chromosomal LAD-LAD segregation and LAD scaffolding at the NE.Competing Interest StatementThe authors have declared no competing interest.