HDAC4 controls senescence and aging by safeguarding the epigenetic identity and ensuring the genomic integrity

Purpose: Define the epigenetic program of HDAC4 Outcome: HDAC4 controls the H3K27me3 of repetitive elements of retroviral origin (ERVs) and the H3K27 deacetylation of typical and super-enhancers found to be activated during senescence. The former response is due to the remodeling of the chromatin that sorrounds ERVs, while the latter is directly mediated by HDAC4 binding to the chromatin and the local deacetylation. Overall design: The chromatin purified from SK-LMS-1 HDAC4KO cells, re-expressing HDAC4, was the control sample. The chromatin purified from SK-LMS-1 HDAC4KO cells, 36h after the removal of HDAC4, was the KO sample. 3 independent ChIP in control and KO samples were perfomed by using anti-H3K27ac, anti-H3K27me3 and anti-HDAC4 antibodies or control IgG. 1/100 input was taken as reference. 3 biological replicates from the control and from the KO samples were independently validated in end-point PCR, pulled-down in accordance to BLUEPRINT requirements, used to prepare ChIP-seq libraries and sequenced.