A novel histone variant H2A.J accumulates in senescent human cells with persistent DNA damage and promotes inflammatory gene expression. Homo sapiens

The senescence of mammalian cells is characterized 1 by a proliferative arrest in response to stress and the expression of an inflammatory phenotype. We discovered that 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 tissue5specific manner. Knock-down of H2A.J inhibited the expression of inflammatory genes that contribute to the senescent-associated secretory phenotype (SASP), and over-expression of H2A.J increased the expression of some of these genes in proliferating cells. H2A.J accumulation may thus promote the signaling of senescent cells to the immune system, and it may contribute to chronic inflammation and the development of diseases with aging.