A HDAC4-HDAC2 complex composes an epigenetic sensor that links the DNA damage response to the senescent program by erasing H2BK120 acetylation [I]

Purpose: Recognize the specific H2BK120ac profile around HDAC4 binding sites in proliferating, pre-senescent, senescent and senescence escaped cells during the accumulation of dsDNA damage, compared to undamaged regions. Outcome: We discovered a novel epigenetic complex formed by HDAC4 and HDAC2 that is involved in monitoring H2BK120 acetylation. The HDAC4/HDAC2 complex, through the dynamic deacetylation of H2BK120, modulates the efficiency of DNA repair by homologous recombination (HR) by controlling the recruitment of BRCA1 and CtIP to the site of lesions. Degradation of HDAC4 during senescence has a dual effect. First, it contributes to super-enhancers activation by limiting HDAC3 activity, and second, it causes the accumulation of DNA damage.