DNA damage promotes HDAC4 nuclear localization and G2/M promoters repression via p53 C-terminal lysisnes

Repression of G2/M promoters after DNA-damage is an active mechanism that requires the p53 tumor suppressor. We have recently found that HDAC4 is recruited on NF-Y-dependent repressed promoters. In this report, we describe the relationship between p53 and HDAC4 recruitment following DNA-damage. (i) HDAC4 shuttles from the cytoplasm into the nucleus following DNA-damage, independently of the activation of p53. (ii) HDAC4 becomes associated to promoters through a p53-dependent mechanism. (iii) The C-terminal Lysines of p53, which are acetylated and methylated, are required for HDAC4 recruitment and transcriptional repression. (iv) TSA treatment, but not HDAC4 functional inactivation, relieves the Adriamycin-mediated repression of G2/M promoters. Our results indicate that HDAC4 is a component of the DNA-damage response, and that post-translational modifications of p53 are important for repression of G2/M genes.