Hmga2 overexpression alters transcription of genes including the targets of Ezh2. (A) A Principal component (PC) analysis based on total gene expression in LSK cells (LSKs) isolated from WT, H, J, HJ, or JE recipient mice (5 for each and mixed for RNA-seq) 4 weeks after tamoxifen injection. (B) Venn diagrams showing upregulated genes between HJ and JE LSKs relative to J. (C) Venn diagrams showing upregulated genes between HJ and JE LSK cells relative to WT. (D) Heatmaps showing the expression of representative genes upregulated in panels B and C. (E) MYC pathway enriched in HJ (top) and JE (bottom) compared with WT. This pathway was not enriched in J (FDR = 0.389). (F) Enrichment plot of G1-S transition (HJ vs J), which represents frequent upregulations of gene sets associated with cell cycle and metabolism in ΔHmga2/JAK2^V617F LSKs (shown in supplemental Tables 3 and 4). (G) Signal activation/inactivation in HJ and JE mice relative to J shown by an upstream analysis. Pathways with z score > |2| in both HJ and JE are shown. (H) CD71⁺Ter119⁺ erythroblasts sorted from BM of 12-week-old WT, H, J, and HJ mice (3 for each) were mixed for RNA-seq. Enrichment of gene sets for regulation of apoptosis (HJ vs J) is shown. (I) GSEA of RNA-seq data for p53-dependent G1 DNA damage response pathway in erythroblasts (HJ vs J). H, ΔHmga2; J, JAK2^V617F; HJ, ΔHmga2/JAK2^V617F; JE, JAK2^V617F/Ezh2^Δ/Δ; NES, normalized enrichment score.