Molecular control of hemoglobin switching

By approximately 6 months of age, the switch from fetal hemoglobin (HbF) to adult hemoglobin (HbA) has been completed. Hemoglobin switching is controlled by a number of enhancers, repressors, and other factors. This figure shows the adult configuration. HbF declines because expression of the gamma globin gene (HBG; designated γγ in the figure) is repressed by a complex that includes BCL11A; this is the principle mechanism for repressing HbF. HbA increases as expression of the beta globin gene (HBB; designated β in the figure) increases. HGB and HBB compete for interaction with the locus control region (LCR), located upstream in the DNA. This competition is regulated by stage-specific transcription factors. Refer to UpToDate for discussion of these transcription factors and transcriptional repressors, as well as other factors including microRNAs (mi-RNAs) such as 15a, 16-1, let-7, LIN28, IGF2BP, and PMRT5.