Higher-order unfolding of satellite heterochromatin is a consistent and early event in cell senescence
UMass Chan Affiliations
Department of Cell and Developmental BiologyDocument Type
Journal ArticlePublication Date
2013-12-16Keywords
AnimalsCell Aging
DNA, Satellite
Epigenesis, Genetic
Heterochromatin
Histones
Humans
Mice
Oxidative Stress
Progeria
Ubiquitin-Protein Ligases
ras Proteins
Cancer Biology
Cell Biology
Cellular and Molecular Physiology
Molecular Genetics
Metadata
Show full item recordAbstract
Epigenetic changes to chromatin are thought to be essential to cell senescence, which is key to tumorigenesis and aging. Although many studies focus on heterochromatin gain, this work demonstrates large-scale unraveling of peri/centromeric satellites, which occurs in all models of human and mouse senescence examined. This was not seen in cancer cells, except in a benign senescent tumor in vivo. Senescence-associated distension of satellites (SADS) occurs earlier and more consistently than heterochromatin foci formation, and SADS is not exclusive to either the p16 or p21 pathways. Because Hutchinson Guilford progeria syndrome patient cells do not form excess heterochromatin, the question remained whether or not proliferative arrest in this aging syndrome involved distinct epigenetic mechanisms. Here, we show that SADS provides a unifying event in both progeria and normal senescence. Additionally, SADS represents a novel, cytological-scale unfolding of chromatin, which is not concomitant with change to several canonical histone marks nor a result of DNA hypomethylation. Rather, SADS is likely mediated by changes to higher-order nuclear structural proteins, such as LaminB1.Source
Originally published as: Swanson EC, Manning B, Zhang H, Lawrence JB. Higher-order unfolding of satellite heterochromatin is a consistent and early event in cell senescence. J Cell Biol. 2013 Dec 23;203(6):929-42. doi:10.1083/jcb.201306073. Link to article on publisher's siteDOI
10.1083/jcb.201306073Permanent Link to this Item
http://hdl.handle.net/20.500.14038/36037PubMed ID
24344186Related Resources
Link to Article in PubMedRights
Copyright 2013 Swanson et al.
Publisher PDF posted as allowed by the publisher's author rights policy at http://www.rupress.org/site/subscriptions/terms.xhtml.
ae974a485f413a2113503eed53cd6c53
10.1083/jcb.201306073