Deletion of the HBB promoter or disruption of the TATA box alters association of globin genes with the LCR. (A) Capture-C profiles of HS3 in clonal populations of WT HUDEP-2 cells (n = 2), HBB promoter deletion cells (n = 2), and TATA box mutation cells (n = 2). The positions of the β-globin locus genes are indicated below the profiles. (B) Proposed model of the molecular mechanism underlying the reversal of globin switching following the removal or disruption of the HBB promoter. In WT adult erythroid cells, the LCR loops to the HBB gene and promotes the expression of the HBB gene. When the promoter is unavailable to the LCR, the LCR loops to the promoter of another β-like globin gene, most commonly the HBG gene, and promotes expression. Created with BioRender.com.