Back to Search
Start Over
Lamin C is required to establish genome organization after mitosis
- Source :
- Genome Biology, Vol 22, Iss 1, Pp 1-27 (2021), Genome Biology
- Publication Year :
- 2021
- Publisher :
- BMC, 2021.
-
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.
- Subjects :
- congenital, hereditary, and neonatal diseases and abnormalities
animal structures
Euchromatin
Nuclear Envelope
QH301-705.5
Mitosis
Biology
QH426-470
Genome
Chromosomes
Mice
Genetics
Animals
Humans
Telophase
Biology (General)
Genomic organization
Cell Nucleus
Regulation of gene expression
Nuclear Lamina
Lamin Type B
integumentary system
Research
Lamin Type A
Chromatin
Lamins
Cell biology
embryonic structures
cardiovascular system
Nuclear lamina
Lamin
Subjects
Details
- Language :
- English
- Volume :
- 22
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Genome Biology
- Accession number :
- edsair.doi.dedup.....2d727b702f44b0eca5731eba60b49cb8