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. 2020 Jun 15;136(15):1735–1747. doi: 10.1182/blood.2019001279

Figure 6.

Figure 6.

Tip60 maintains the acetylation of H2A.Z to activate Myc target genes. (A) An integrated view of Tip60 occupancy and acH2A.Z, H2A.Z, and H3K27me3 enrichment around TSS (TSS, ±4 kb) in ChIP-seq analysis using wild-type fetal c-Kit+ cells. Genes were ordered according to the expression levels (line plots) from high (top) to low (bottom). The color scale represents changes in signal intensity for each antibody. (B) Cloud plots represent all (left) and Tip60-bound (right) genes, according to the corresponding acH2A.Z/H2A.Z ratio from ChIP-seq and the gene expression level from RNA-seq. Correlation analysis between the acH2A.Z/H2A.Z ratio and the gene expression level is shown. The blue line represents the polynomial regression curve (R2 = 0.7). The red line represents a theoretical linear regression curve (y = x). Genes with a high acH2A.Z/H2A.Z ratio (>2) acH2A.Z and a high RNA level (log2 FPKM >5) are in red rectangles. Tip60-bound genes were identified based on Tip60 enrichment at the proximal promoter region (−1 kb, +100 bp from the TSS). (C) Mean plot of acH2A.Z, H2A.Z, acH2A.Z/H2A.Z ratio, acH3K27, and H3K27me3 enrichment based on relative distance from Tip60-bound proximal promoter regions in both control (purple) and Tip60Δ/Δ fetal c-Kit+ cells (red). Statistical analyses were performed using the Mann-Whitney Wilcoxon method. (D) Myc target genes (n = 816) were identified to be transcribed in both control and Tip60Δ/Δ fetal LSK cells in the RNA-seq analysis. The x-axis indicates log2-fold change in acH2A.Z/H2A.Z ratio at proximal promoter regions induced by Tip60 deletion and the y-axis indicates log2-fold change in gene expression level. DNA repair–related genes (blue) and cell-cycle–related genes (pink) with significant downregulation in their expression levels (P < .05) are labeled. Myc target genes were obtained from the gene sets described in Figure 5A. DNA repair– and cell-cycle–related genes were obtained from Gene Ontology categories GO:0006281 and GO:0007049, respectively. (E) Tip60 maintains HSCs through acetylation of H2A.Z, to activate Myc target genes that regulate cell-cycle and DNA repair processes. FPKM, fragments per kilobase per million.