Stress‐induced and ATF7‐dependent epigenetic change influences cellular senescence

Autor:	Yang Liu, Toshio Maekawa, Masafumi Muratani, Shunsuke Ishii, Binbin Liu, Keisuke Yoshida, Bruno Chatton
Rok vydání:	2019
Předmět:	Male Longevity Activating transcription factor p38 Mitogen-Activated Protein Kinases Epigenesis Genetic Histones Mice 03 medical and health sciences Cyclin-dependent kinase Sciences du Vivant [q-bio]/Biologie cellulaire Genetics Animals Epigenetics Promoter Regions Genetic Cells Cultured Cellular Senescence Cyclin-Dependent Kinase Inhibitor p16 030304 developmental biology 0303 health sciences biology Kinase Cell Biology genetics metabolism Activating Transcription Factors Cell biology Chromatin Mice Inbred C57BL Oxidative Stress Histone biology.protein Phosphorylation Female CDK inhibitor Protein Binding
Zdroj:	Genes to Cells. 24:627-635
ISSN:	1365-2443 1356-9597
Popis:	Cellular senescence plays an important role in aging and is induced by cyclin-dependent kinase (Cdk) inhibitors that accumulate following stresses during aging. However, the underlying mechanism remains elusive. Herein, we demonstrate that activating transcription factor 7 (ATF7), the stress-responsive recruiter of histone H3K9 di- and trimethyltransferases, functions in the accumulation of Cdk inhibitors. Atf7-deficient (Atf7-/- ) mice have a shorter lifespan than wild-type (WT) mice. Levels of p16Ink4a Cdk inhibitor mRNA increased with age more rapidly in Atf7-/- mice than in WT animals. ATF7 binds to the p16Ink4a gene promoter and was released with age. Consistently, histone H3K9me2 levels on the p16Ink4a gene promoter were lower in Atf7-/- mice than in WT animals. Similar results were obtained when Atf7-/- and WT mouse embryonic fibroblasts (MEFs) were cultured under 20% oxygen conditions, which induces cellular senescence via oxidative stress. Phosphorylation of ATF7 by p38 was also increased with the passage of MEFs, consistent with previous observations that ATF7 phosphorylation by p38 induces its release from chromatin. These results indicate that stress-induced and ATF7-dependent epigenetic changes on p16Ink4a genes play an important role in cellular senescence.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::de4631c6dfc11fdb0fbfbeff42f8522a https://doi.org/10.1111/gtc.12713 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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