A model for human γ-to-β globin switching and γ-globin reactivation in adult hematopoietic cells. In fetal life, the human γ-globin genes are preferentially activated by interactions between the β-LCR and the γ-globin genes mediated by transcription factors and chromatin remodeling complexes. The details of these complexes at this time are unknown. In adult-type hematopoietic cells, chromatin remodeling complexes repress γ-globin transcription, change the conformation of the β-globin locus by binding to the intergenic γ_δ sequences, and favor interactions between the β-LCR and the downstream β-globin gene. PYR complex, shown here binding to the region upstream of the human δ-globin gene (and included in the Corfu deletion) with Ikaros as its DNA-binding subunit, is a known adult erythroid stage_specific chromatin remodeling complex that may function in this process. The subunits of PYR complex are shown. These include SWI/SNF subunits, parts of an ATP-generated chromatin remodeling complex that activate gene transcription; NURD subunits, parts of a repressive chromatin remodeling complex with HDACs; and Ikaros as the DNA-binding subunit that holds the complex together (11).