Histone variant H2A.J accumulates in senescent cells and promotes inflammatory gene expression

被引：138

作者：

Contrepois, Kevin ^{[1
,2
]}

Coudereau, Clement ^{[1
]}

Benayoun, Berenice A. ^{[2
,3
]}

Schuler, Nadine ^{[4
]}

Roux, Pierre-Francois ^{[5
]}

Bischof, Oliver ^{[5
]}

Courbeyrette, Regis ^{[1
]}

Carvalho, Cyril ^{[1
]}

Thuret, Jean-Yves ^{[1
]}

Ma, Zhihai ^{[2
]}

Derbois, Celine ^{[6
]}

Nevers, Marie-Claire ^{[7
]}

Volland, Herve ^{[7
]}

Redon, Christophe E. ^{[8
]}

Bonner, William M. ^{[8
]}

Deleuze, Jean-Francois ^{[6
]}

Wiel, Clotilde ^{[9
]}

Bernard, David ^{[9
]}

Snyder, Michael P. ^{[2
]}

Ruebe, Claudia E. ^{[4
]}

Olaso, Robert ^{[6
]}

Fenaille, Francois ^{[10
]}

Mann, Carl ^{[1
]}

机构：

[1] Univ Paris Saclay, Univ Paris Sud, I2BC, CEA,CNRS, F-91198 Gif Sur Yvette, France

[2] Stanford Univ, Dept Genet, Stanford, CA 94305 USA

[3] Stanford Univ, Paul F Glenn Labs Biol Aging, Stanford, CA 94305 USA

[4] Saarland Univ, Dept Radiat Oncol, D-66421 Homburg, Saar, Germany

[5] Inst Pasteur, Lab Nucl Org & Oncogenesis, Dept Cell Biol & Infect, INSERM,U933, F-75015 Paris, France

[6] CEA, CNG, F-91057 Evry, France

[7] Univ Paris Saclay, INRA, CEA, SPI, F-91191 Gif Sur Yvette, France

[8] NCI, Mol Pharmacol Lab, CCR, NIH, Bethesda, MD 20892 USA

[9] Univ Lyon, Ctr Leon Berard, Ctr Rech Cancerol Lyon, CNRS,UMR5286,Inserm,U1052, F-69008 Lyon, France

[10] Univ Paris Saclay, Lab Etud Metab Medicaments, Serv Pharmacol & Immunoanal, MetaboHUB Paris,CEA,IBITECS,UMR 0496, F-91191 Gif Sur Yvette, France

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

美国国家卫生研究院;

关键词：

CELLULAR SENESCENCE; CANCER; MICE; SIDE;

D O I：

10.1038/ncomms14995

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The senescence of mammalian cells is characterized by a proliferative arrest in response to stress and the expression of an inflammatory phenotype. Here we show that histone H2A.J, a poorly studied H2A variant found only in mammals, accumulates in human fibroblasts in senescence with persistent DNA damage. H2A.J also accumulates in mice with aging in a tissue-specific manner and in human skin. Knock-down of H2A.J inhibits the expression of inflammatory genes that contribute to the senescent-associated secretory phenotype (SASP), and over expression of H2A.J increases the expression of some of these genes in proliferating cells. H2A.J accumulation may thus promote the signalling of senescent cells to the immune system, and it may contribute to chronic inflammation and the development of aging-associated diseases.

引用

页数：18

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