Research on epigenetic regulation of aging and cancer by CHD8/histone H1 complex

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We recently have found that a chromatin remodeling factor CHD8 suppresses p53 function by recruiting the linker histone H1 on chromatin, and expected that a CHD8/histone H1 complex may play an important role in chromatin remodeling in cellular senescence. First, we investigated the effect of CHD8 overexpression on cellular senescence in normal cells, and revealed that forced expression of CHD8 inhibits p53-induced cellular senescence. We next generated CHD8-inducible transgenic mice, and revealed that CHD8 has a potent transformating activity. In normal aging or premature aging mice, we found that the expression level of CHD8/histone H1 is markedly decreased. Furthermore, we found that cellular senescence is induced in histone H1-knockdown cells or the cells derived from CHD8-knockout mice. Taken together, it is expected that CHD8 not only has anti-aging effect, but also functions as an oncogene.