Histon Variante H2A.J
Histone variant H2A.J involved in persistent DNA damage signaling triggers senescence-associated inflammatory cytokine secretion
The senescence of mammalian cells is characterized by a proliferative arrest in response to stress and the expression of an inflammatory phenotype. 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.
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Immunomodulatory Effects of Histone Variant H2A.J in Ionizing Radiation Dermatitis. Tewary G, Freyter B, Al-Razaq MA, Auerbach H, Laschke MW, Kübelbeck T, Kolb A, Mangelinck A, Mann C, Kramer D, Rübe CE. Int J Radiat Oncol Biol Phys. 2024 Mar doi: 10.1016/j.ijrobp.2023.09.022 PMID: 37758068
Role of Histone Variant H2A.J in Fine-Tuning Chromatin Organization for the Establishment of Ionizing Radiation-Induced Senescence. Abd Al-Razaq MA, Freyter BM, Isermann A, Tewary G, Mangelinck A, Mann C, Rübe CE. Cells. 2023 Mar doi: 10.3390/cells12060916 PMID: 36980257
Cultured Human Foreskin as a Model System for Evaluating Ionizing Radiation-Induced Skin Injury. Hippchen Y, Tewary G, Jung D, Schmal Z, Meessen S, Palm J, Rübe CE.Int J Mol Sci. 2022 Aug; doi: 10.3390/ijms23179830 PMID: 36077226
Human skin aging is associated with increased expression of the histone variant H2A.J in the epidermis.Rübe CE, Bäumert C, Schuler N, Isermann A, Schmal Z, Glanemann M, Mann C, Scherthan H. NPJ Aging Mech Dis. 2021 Apr 1;7(1):7. PMID: 33795696
Histone Variant H2A.J Marks Persistent DNA Damage and Triggers the Secretory Phenotype in Radiation-Induced Senescence. Isermann A, Mann C, Rübe CE. Int. J. Mol. Sci. 2020, 21(23), 9130. PMID: 33266246
Histone variant H2A.J accumulates in senescent cells and promotes inflammatory gene expression. Contrepois K, Coudereau C, Benayoun BA, Schuler N, Roux PF, Bischof O, Courbeyrette R, Carvalho C, Thuret JY, Ma Z, Derbois C, Nevers MC, Volland H, Redon CE, Bonner WM, Deleuze JF, Wiel C, Bernard D, Snyder MP, Rübe CE, Olaso R, Fenaille F, Mann C. Nat Commun. 2017 May 10;8:14995. PMID: 28489069
