FOXA1 mediates p16(INK4a) activation during cellular senescence.

ABSTRACT: Mechanisms governing the transcription of p16(INK4a), one of the master regulators of cellular senescence, have been extensively studied. However, little is known about chromatin dynamics taking place at its promoter and distal enhancer. Here, we report that Forkhead box A1 protein (FOXA1) is significantly upregulated in both replicative and oncogene-induced senescence, and in turn activates transcription of p16(INK4a) through multiple mechanisms. In addition to acting as a classic sequence-specific transcriptional activator, FOXA1 binding leads to a decrease in nucleosome density at the p16(INK4a) promoter in senescent fibroblasts. Moreover, FOXA1, itself a direct target of Polycomb-mediated repression, antagonizes Polycomb function at the p16(INK4a) locus. Finally, a systematic survey of

SUBMITTER: Li Q 

PROVIDER: S-EPMC3604725 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature