The role of heptad TFs in regulating lineage-specific gene expression. (A) Schematic of the bioinformatic strategy used to derive regions showing differential heptad factor binding: (i) Candidate regulatory elements (REs) with binding of at least 2 heptad factors were chosen in the 4 cell types; and (ii) DiffBind was used to filter for regions showing differential enrichment for heptad factors with an FDR <0.05. To perform DiffBind analysis only HSC-MPP (HSC), GMP, and MEP populations were chosen. (iii) These DEH regions were linked to genes either directly (present across a 10 kb promoter region) or indirectly (distal links using significant [FDR <0.01] H3K27ac- HiChIP interactions), and (iv) used as input for multiple characterization assays. (B) Gene set enrichment analysis (GSEA) plots showing enrichment of derived gene sets in pairwise gene expression comparisons: (i) DEHG^HSC (genes linked to DEH regions in HSC-MPP) enriched in HSC-MPP with respect to GMP, (ii) DEHG^GMP enriched in GMP with respect to HSC-MPP, (iii) DEHG^HSC enriched in HSC-MPP with respect to MEP, and (iv) DEHG^MEP enriched in MEP with respect to HSC-MPP. (C) Scoring cell-specific DEHGs along a (i) single-cell expression map reveals localized enrichment of expression: (ii) DEHG^HSC, (iii) DEHG^GMP, and (iv) DEHG^MEP. ES, enrichment score; NES, normalized enrichment score; q, FDR q value from GSEA.