Bach1 inhibits oxidative stress–induced cellular senescence by impeding p53 function on chromatin

Oxidative stress can lead to cellular senescence, in a p53-dependent pathway. Bach1, a transcription factor that regulates the response to oxidative stress, is now shown to inhibit senescence induced by high oxygen concentrations or by Ras. Bach1 is recruited to a subset of p53 target genes and contributed to impeding p53 action by promoting histone deacetylation. Cellular senescence is one of the key strategies to suppress expansion of cells with mutations. Senescence is induced in response to genotoxic and oxidative stress. Here we show that the transcription factor Bach1 (BTB and CNC homology 1, basic leucine zipper transcription factor 1), which inhibits oxidative stress-inducible genes, is a crucial negative regulator of oxidative stress–induced cellular senescence. Bach1 -deficient murine embryonic fibroblasts showed a propensity to undergo more rapid and profound p53-dependent premature senescence than control wild-type cells in response to oxidative stress. Bach1 formed a complex that contained p53, histone deacetylase 1 and nuclear co-repressor N-coR. Bach1 was recruited to a subset of p53 target genes and contributed to impeding p53 action by promoting histone deacetylation. Because Bach1 is regulated by oxidative stress and heme, our data show that Bach1 connects oxygen metabolism and cellular senescence as a negative regulator of p53.