Extended Data Fig. 7: Capture C and CUT&RUN analysis of VHL-disrupted erythroblasts (linked to main Fig. 3).

Normal adult donor CD34⁺ cells were transfected with RNP containing Cas9 + VHL sgRNAs or NT sgRNA, after which erythroid differentiation was induced. a, CUT&RUN and ATAC-seq analysis of the extended α-like globin locus in day 11 erythroblasts. Biological replicate experiments were performed using VHL sgRNAs 1 and 2. A weak VHL-independent HIF1β signal with no underlying HRE motif is present in NPRL3, which harbors a multicomponent α-globin enhancer. Most likely, this signal represents nonspecific micrococcal nuclease digestion associated with open chromatin. b, Analysis of the ZBTB7A locus, as described for panel a. The low-magnitude VHL-independent HIF1β signal with no underlying HRE motif in the promoter region most likely represents nonspecific micrococcal nuclease digestion associated with open chromatin. c, Capture-C analysis to identify chromatin looping, performed at day 11 of erythroid differentiation. Tracks show data from two biological replicate experiments using CD34⁺ HSPCs from different donors. Anchors are indicated at the BGLT3, HBBP1, and HS3 regions. Main Fig. 3b shows combined data from these experiments. d, CUT&RUN analysis and Capture C analysis of the BCL11A locus with an anchor at the promoter. The intron 2 erythroid-specific enhancer is indicated with an asterisk.