期刊
CELL REPORTS
卷 22, 期 13, 页码 3480-3492出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.03.002
关键词
-
类别
资金
- NIH/NIA [R37 AG016694, P01 AG051449]
- NIH [T32 GM007601, F31 AG043189]
- NIH/NIGMS [P30 GM0103410]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007601] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG016694, P01AG051449] Funding Source: NIH RePORTER
Polycomb group (PcG) factors maintain facultative heterochromatin and mediate many important developmental and differentiation processes. EZH2, a PcG histone H3 lysine-27 methyltransferase, is repressed in senescent cells. We show here that downregulation of EZH2 promotes senescence through two distinct mechanisms. First, depletion of EZH2 in proliferating cells rapidly initiates a DNA damage response prior to a reduction in the levels of H3K27me3 marks. Second, the eventual loss of H3K27me3 induces p16 (CDKN2A) gene expression independent of DNA damage and potently activates genes of the senescence-associated secretory phenotype (SASP). The progressive depletion of H3K27me3 marks can be viewed as a molecular timer'' to provide a window during which cells can repair DNA damage. EZH2 is regulated transcriptionally by WNT and MYC signaling and posttranslationally by DNA damage-triggered protein turnover. These mechanisms provide insights into the processes that generate senescent cells during aging.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据