Dnmt3a^R878H/+ chromatin state is altered by cooperating Npm1^cA mutation in a cell-type-specific manner. (A) Experimental design. (B) Principal component analysis of ATAC-seq data from HSC and MPP^G/M cells with genotypes Mx-Cre, Dnmt3a^R878H/+, Npm1^cA/+, and Dnmt3a^R878H/+;Npm1^cA/+. Principal components were calculated based on the top 900 differentially accessible promoter peaks across all conditions, ranked by FDR. Data were collected from 2 to 3 pooled mice for each replicate (1 to 2 per condition). (C) Venn diagrams representing overlapping promoter accessibility gain (left) or loss (right) between Dnmt3a^R878H/+; Npm1^cA/+ vs Dnmt3a^R878H/+ HSCs and MPP^G/M cells. (D) Pathway enrichment of the 343 promoters with increased accessibility in Dnmt3a^R878H/+;Npm1^cA/+ vs Dnmt3a^R878H/+ HSCs. The low number of accessible promoter gains in MPP^G/M cells (39 promoters) precluded pathway enrichment analysis. (E) Transcription factor binding site enrichment in promoters with increased accessibility. (F) Pathway enrichment of the 97 promoters with decreased accessibility in Dnmt3a^R878H/+;Npm1^cA/+ vs Dnmt3a^R878H/+ HSCs, and the 281 promoters with decreased accessibility in Dnmt3a^R878H/+;Npm1^cA/+ vs Dnmt3a^R878H/+ MPP^G/M cells. (G) Transcription factor binding site enrichment in promoters with decreased accessibility.