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

Kévin Contrepois, Clément Coudereau, Bérénice A. Benayoun, Nadine Schuler, Pierre-François Roux, Oliver Bischof, Régis Courbeyrette, Cyril Carvalho, Jean-Yves Thuret, Zhihai Ma, Céline Derbois, Marie-Claire Nevers, Hervé Volland, Christophe E. Redon, William M. Bonner, Jean-François Deleuze, Clotilde Wiel, David Bernard, Michael P. Snyder, Claudia E. Rübe, Robert Olaso, François Fenaille and Carl Mann ()
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Kévin Contrepois: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay
Clément Coudereau: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay
Bérénice A. Benayoun: Stanford University
Nadine Schuler: Saarland University
Pierre-François Roux: Institut Pasteur/INSERM U933, Laboratory of Nuclear Organization and Oncogenesis
Oliver Bischof: Institut Pasteur/INSERM U933, Laboratory of Nuclear Organization and Oncogenesis
Régis Courbeyrette: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay
Cyril Carvalho: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay
Jean-Yves Thuret: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay
Zhihai Ma: Stanford University
Céline Derbois: CEA, CNG
Marie-Claire Nevers: CEA, Service de Pharmacologie et Immunoanalyse (SPI), INRA, Université Paris-Saclay
Hervé Volland: CEA, Service de Pharmacologie et Immunoanalyse (SPI), INRA, Université Paris-Saclay
Christophe E. Redon: Laboratory of Molecular Pharmacology, C.C.R., N.C.I., N.I.H.
William M. Bonner: Laboratory of Molecular Pharmacology, C.C.R., N.C.I., N.I.H.
Jean-François Deleuze: CEA, CNG
Clotilde Wiel: Inserm U1052, Centre de Recherche en Cancérologie de Lyon, CNRS UMR5286, Centre Léon Bérard, Université de Lyon
David Bernard: Inserm U1052, Centre de Recherche en Cancérologie de Lyon, CNRS UMR5286, Centre Léon Bérard, Université de Lyon
Michael P. Snyder: Stanford University
Claudia E. Rübe: Saarland University
Robert Olaso: CEA, CNG
François Fenaille: CEA, IBITECS, Service de Pharmacologie et d'Immunoanalyse, UMR 0496, Laboratoire d'Etude du Métabolisme des Médicaments, MetaboHUB-Paris, Université Paris Saclay
Carl Mann: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay

Nature Communications, 2017, vol. 8, issue 1, 1-18

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms14995

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