Constructs used in the study and location of HPFH breakpoints in the human β-globin locus. The constructs comprising the LCR and the ^Aγ gene with or without the HPFH enhancers are shown at the top. The human β-globin locus is shown below the constructs, indicating the position of the LCR and the order of the genes. The HPFH-1, HPFH-2, HPFH-3, and HPFH-6 deletions are shown below the locus. Hatched boxes indicate the core enhancer elements associated with the HPFH breakpoints (not to scale). Solid vertical arrows indicate hematopoietic-specific DNase I hypersensitive sites (HS), and the gray arrow indicates a ubiquitous HS site.