Extended Data Fig. 4: HIF1α binds the BGLT3 gene in the β-like globin gene cluster (linked to main Fig. 2).

a, HIF1α CUT&RUN analysis of VHL^−/− HUDEP-2 cells (clone 1) and primary erythroblasts generated from VHL-depleted CD34⁺ cells. The tracks show HIF1α occupancy at its known target genes LDHA and BNIP3. b, The top panels show heatmaps of high-confidence genome-wide CUT&RUN peaks for HIF1α and HIF2α occupancy in primary erythroblasts generated by in vitro differentiation of CD34⁺ HSPCs that were transfected with RNPs consisting of Cas9 + VHL sgRNA1 or NT sgRNA and in A549 adenocarcinoma cells transfected with the same RNPs. The lower panels show genome-wide targeted-motif footprint analysis of CUT&RUN peaks indicating the cut probability of each base surrounding or within HIF-binding hypoxia response elements (HRE; ACGTG). c, CUT&RUN analysis of HIF1α occupancy at BGLT3 (left panels) or LDHA (right panels) in VHL^−/− HUDEP-2 cells (clone 2) with adenine base editor–induced mutations in BGLT3 HRE motifs A and/or B. d, Genome-wide CUT&RUN analysis of HIF1α in bulk VHL^−/− HUDEP-2 cells (clone 2) edited with NT sgRNA (x-axis) or sgRNAs targeting BGLT3 motifs A and B (y-axis). Each dot represents an individual high-confidence HIF1α peak. The BGLT3 HIF1α occupancy peak is indicated by the red dot. e, Heat maps showing Pearson correlation coefficients of genome-wide, normalized HIF1α CUT&RUN peak patterns in VHL^−/− HUDEP-2 cell clones 1 (left) and 2 (right) ± mutations in BGLT3 HIF-binding motifs A and/or B, as described in main Fig. 2h and I and in panels c and d of this figure.