Hemoglobin switching's surprise: the versatile transcription factor BCL11A is a master repressor of fetal hemoglobin. (August 2015)

• Record Type: Journal Article
• Authors: Bauer, Daniel E; Orkin, Stuart H
• Is Part Of: Current opinion in genetics & development. Volume 33(2015)
• Page Start: 62
• Page End: 70
• Publication Date: 2015-08
• Subjects: Genetics -- Periodicals; Developmental biology -- Periodicals; Developmental genetics -- Periodicals; 576.5
• DOI: 10.1016/j.gde.2015.08.001
• Languages: English
• ISSNs: 0959-437X

Abstract

Abstract : The major disorders of β-globin, sickle cell disease and β-thalassemia, may be ameliorated by expression of the fetal gene paralog γ-globin. Uncertainty regarding the mechanisms repressing fetal hemoglobin in the adult stage has served as a puzzle of developmental gene regulation as well as a barrier to rational therapeutic design. Recent genome-wide association studies implicated the zinc-finger transcriptional repressor BCL11A in fetal hemoglobin regulation. Extensive genetic analyses have validated BCL11A as a potent repressor of fetal hemoglobin level. Studies of BCL11A exemplify how contextual gene regulation may often be the substrate for trait-associated common genetic variation. These discoveries have suggested novel rational approaches for the β-hemoglobin disorders including therapeutic genome editing.