FLI1, ERG, GATA2, RUNX1, SCL/TAL1, LYL1, and LMO2 form a densely interconnected network and are associated with differential gene expression. (A) Density plots for ChIP-seq reads in hCD34⁺ HSPCs displayed in the UCSC genome browser with corresponding RNA-seq expression shows overlapping binding of the heptad at the ERG +85 hematopoietic stem cell enhancer (also see supplemental Figure 2). (B) The heptad TFs show binding at each constituent locus (also see Figure 5A; supplemental Figure 2). The edges show binding of TF protein (node) at the target gene. (C) Cumulative density distribution illustrating the number of unique sites associated with a gene bound by least 1 TF and having at least 1 site bound by 1 to 7 TFs. For example, the ERG locus shown in panel A is associated with the binding of 7 TFs at the +85 enhancer (red curve) and has an additional 4 binding sites at approximately +70, +84, +120, and + 175. Thecumulative density distribution shows that heptad-associated genes are bound at a median of 4 additional sites, whereas genes associated with only 1 TF have a median of 1 additional bound region. (D) Correlation of the GREAT output with Mouse Genome Informatics and Molecular Signatures databases for phenotype-/disease-type associations (see supplemental Table 4 for the full set of enriched terms). (E) GSEA shows significant enrichment for the expression of genes that are targets of the heptad. (F) Correlation of gene expression levels quantified by RNA-seq and divided into expression quartiles with histone marks around the transcription start sites (q1 = lowest expressed; q4 = highest expressed) (also see supplemental Figures 4-6).