Figure 3.
Heptad regulatory circuits are remodeled during myeloid progenitor development. (A) Stepwise identification of potential regulatory regions interacting with the ERG promoter. (i) Raw HiChIP contact matrix, CTCF, H3K4me3, H3K27ac, IgG, RNA-seq, and significant H3K27ac HiChIP interactions (false discovery rate [FDR] ≤ 0.01) at the ERG locus (GRCh38 chr21:37370238-39198738). The ERG promoter is indicated by the green arrow (only those HiChIP interactions where both interacting ends were found at the given locus are shown). (ii) Magnified view of the ERG locus, with regulators identified to loop to the ERG proximal promoter shown as red triangles. (iii) FLI1, ERG, GATA2, RUNX1, TAL1, LYL1, and LMO2 peaks at the defined regulators in each individual cell type. The peaks shown are RPKM-normalized and white boxes indicate presence of a computationally called ChIP-seq peak at the specific region. (B) Summary plot of gene regulatory interactions across the heptad genes. (i) Individual heptad gene loci with identified regulators indicated by red markers. (ii) Dot plots showing regulatory regions as rows and the 4 cell types as columns, with size of the dot indicating number of heptad factors bound and black color indicating the presence of an active regulatory link to the promoter (using H3K27ac HiChIP). Promoters are underlined. (iii) Bar plots with individual replicates showing average log2 counts of relevant heptad gene expression in the 4 cell types (GSE75384).