Heptad-bound miRNA modulate components of the heptad and their target genes. (A) FLI1, ERG, GATA2, RUNX1, SCL/TAL1, LYL1, and LMO2 form a densely interconnected core circuit with multiple, positive-feedback loops. The heptad TFs are illustrated by square nodes and interactions (green edges) between heptad TFs, and heptad coding genes are illustrated (as detailed in Figure 5B). Genes simultaneously bound by the heptad TFs are illustrated as orange hexagons and miRNAs as red circles, whereas these interactions are shown as black edges. Potential posttranscriptional regulatory interactions between miRNAs and gene transcripts (messenger RNAs) are shown as red edges. The size of the circles representing each miRNA in the network is proportionate to their normalized expression level in CD34⁺ cells. A number of miRNAs form feedback loops with ERG, FLI1, and GATA2. (B) Hematopoietic phenotypes and signatures were enriched (using GREAT) in cluster 2 but not in cluster 1. (C) The numbers of genes corresponding to normal/abnormal hematopoiesis in the ingenuity pathway analysis are enriched in cluster 2 (also see supplemental Figure 9).