(A) Schematic comparison of S. cerevisiae EAF1 and D. melanogaster DOM-A. Conserved domain structure is highlighted, (B) Barplot showing the average fraction of acetylated peptide (over non-acetylated) (n = 3 for B, n = 4 for all the others) for 4 residues in histone H4 tail (K5, K8, K12, K16) upon knock-down of the proteins indicated on the x-axis. Error bars represent SEM. (C) Heatmap shows scaled methylation levels for various histone H3 residues (measured by mass-spectrometry) in cells treated with dsRNA against GST or GFP (CTRL), H2A.V, DOM-A (A), DOM-B (B) and TIP60. Individual biological replicates are shown. Rows and columns are clustered based on Euclidean distance. (D) Barplot showing the average fraction of methylated peptide (over non-methylated) (n = 3 for B, n = 4 for all the others) for H3K27 upon knock-down of the proteins indicated on the x-axis. Error bars represent SEM. (E) Same as (C) but showing scaled methylation levels for histone H4K20 residue (F) Heatmap showing spearman’s correlation coefficients between replicates and dsRNA treatments calculated for H4K12ac ChIPseq normalized coverage signal around the Transcription Start Site (TSS) (±2000 bp) (N = 10139). Clustering is based on Euclidean distance. Individual biological replicates are shown. (G) Composite plot showing spike-in and input normalized H4K12ac coverage around Transcription Start Sites (TSS) for genes not-regulated (not), up-regulated (up), downregulated (down) in the knock-down of DOM-A (left panel) or TIP60 (right panel) (N provided in Figure 2—figure supplement 1; Figure 2—figure supplement 1B). Each line represents the average coverage (n = 3 biological replicates) of H4K12ac in Kc167 cells treated with dsRNA against GST/GFP. (H) Violin-boxplot showing log2 fold-change in H4K12ac signal (averaged across a 4000 bp window around the TSS) between DOM-A or TIP60 and control RNAi. log2 fold-changes were calculated for the following pairs (A1 or Tip60_1 vs GST; A1.2 or Tip60_1.2 vs GST.2; A2 or Tip60_2 vs GFP). In the left panel, all genes measured by RNAseq are considered (N = 10139). In the central and right panels, genes are divided in not-, up- and down-regulated classes as in (G). (I) Table listing calculated p-values (one-sample t-test, two sided) for the differences shown in the left panel of (H). n = 3 biological replicates are considered. Each replicate is a single value representing the median of log2 fold-change [calculated as in H] across all genes analyzed. (J) Table listing calculated p-values (linear regression) for the comparisons depicted in Figure 4E.