A model of fetal hemoglobin (Hb) regulation. The upstream enhancer locus control region (LCR) preferentially interacts with the γ-globin genes to produce the γ-globin chains that assemble with α-globin chains to constitute the heterotetrametric fetal Hb (left). At baseline, ZBTB7A represses the γ-globin genes and helps maintain globin chain balance.87 To switch from fetal to adult Hb, BCL11A and ZBTB7A independently repress the transcription of the γ-globin genes to favor the interaction between the LCR and the β-globin gene (right), producing β-globin chains that associate with α-globin chains in the definitive molecule. BCL11A requires both proximal promoter and long-range interactions to carry out its activity. Professional illustration by Somersault18:24.
