Fig. 4

HDAC4 supervises enhancers and super-enhancers activated early during senescence. a (Left, marked as “GLOBAL”) Heat-map of the 97,831 H3K27ac and the corresponding H3K27me3 signals in the indicated SK-LMS-1 cells; (right, marked as “FC > 2”) heat-map of the 4441 H3K27ac peaks displaying an overall signal ratio (KO/wt) > 2 and the corresponding H3K27me3 signals in the indicated SK-LMS-1 cells. The analysis was performed in a region of ± 15Kb around peak summit. b Genomic distribution of all the H3K27ac and H3K27me3-enriched peaks (top panel), or only of those associated with a FC > 2, as indicated and shown in a. c Histogram representing the percentage of hyper-acetylated (green bar) or demethylated (light blue) H3K27 peaks in SK-LMS-1/HDAC4^−/− cells and falling in the indicated genomic elements or displaying the indicated epigenomic features. The genome coverage of each element is indicated by gray bars. d Histogram representing the enrichment of each element described in Fig. 4c with respect to the expected distribution calculated according to the genome coverage. e Histogram representing the percentage of HDAC4 peaks falling in WT cells in correspondence to the indicated genomic elements or displaying the indicated epigenomic features in HDAC4^−/− cells. f Motif analysis of 91 HDAC4-gained SES for putative transcription factor binding sites. Motifs with p value< 0.5 × 10⁻⁴ were selected. g (Left) Detailed view of 2 representative SES (AKR1E2 and VEGFC associated SES) directly bound by HDAC4 in SK-LMS-1 WT cells in correspondence to H3K27ac-defined SES activated after HDAC4 depletion. (Right) Detailed view of 2 representative SES (IL1B and CXCL8 associated SES) not directly bound by HDAC4 in SK-LMS-1 WT cells, but found activated after HDAC4 depletion