a–c, 200 bp at the functional cores of DHSs h+55, h+58 and h+62 defined by HMM states (active, red; repressive, green). HbF enrichment scores are shown by grey lines and circles. HbF indel enrichment per nucleotide based on amplicon genomic sequencing of sorted cells exposed to either sgRNA-1617 (top) or -1621 (bottom) is shown. Common SNPs (MAF > 1%) are shown with dotted lines with HbF-low allele in blue and HbF-high allele in red; no common SNPs are present at the h+58 region. JASPAR motifs (P < 10−4) are depicted in black except for those with allele-specific significance depicted by allelic colour. Selected motifs annotated by transcription factor on the basis of known erythroid-specific function or genomic position. Motif LOGOs at key positions with motif scores P < 10−3 as described in text. Dotted boxes show regions of highest HbF enrichment score at each core with underlying predicted motifs. Orthologous sequences are listed from representative primates and nonprimates of distributed phylogeny. PhyloP (scale from −4.5 to 4.88) and PhastCons (from 0 to 1) estimates of evolutionary conservation among 100 vertebrates are shown. An arrow indicates a 144 bp insertion in the mouse genome relative to the human reference adjacent to the orthologous GATA1 motif at h+58.