Suz12 and Jarid2 share common H3K27me3-marked target genes in HSPCs. (A) Plots comparing gene expression profiles (shown as LFC) of Suz12-depleted (x-axis, n = 4 samples) vs Jarid2-depleted (y-axis, n = 7 samples) HSPCs compared with separate NS controls (n = 2 to 3) using RNA-seq data shown in Figure 5. Each dot represents a gene, with the size of the dot corresponding to significance of differential expression and the color corresponding to the rank of the H3K27me3 enrichment (adult HSPCs at left, fetal HSPCs at right). The enrichment of the gene ranked halfway through the list (median H3K27me3 enrichment) is gray and the genes that are H3K27me3-enriched or -depleted are colored increasingly red or cyan, respectively. Larger dots, indicating more significant differences in expression, are predominantly found for genes that are red (most H3K27me3 enriched), and these are generally upregulated in both Jarid2 and Suz12 knockdown compared with negative controls (upper right quadrant). (B) Box plots showing that genes that are upregulated when Suz12 and Jarid2 are depleted are enriched for H3K27me3 (log2 H3K27me3/input) using adult HSPC H3K27me3 ChIP-seq data. Genes were divided into those that were upregulated in Suz12 (at left) or Jarid2 (at right) knockdown HSPCs compared with controls (positive LFC; P < .01) or those that were not differentially expressed by Suz12 or Jarid2 knockdown (non DE; P > .01). These genes were scored for their H3K27me3 enrichment in adult HSPCs (y-axis). There was a significantly higher H3K27me3 enrichment for genes that are upregulated compared with genes not differentially expressed after both Suz12 knockdown (P = 1.5 × 10−67) and Jarid2 knockdown (P = 5.2 × 10−17).