Hemoglobin subunit gamma gene promoter (HBG1/HBG2 gene promoter)

The HBG1 and HBG2 gene promoters are upstream regulatory DNA sequences that control the transcription of the gamma-globin genes, HBG1 (A-gamma) and HBG2 (G-gamma), which are components of fetal hemoglobin (HbF)[4][5]. These genes are expressed primarily during fetal development and are normally silenced after birth as hemoglobin switching occurs. Disruption or editing of specific transcription factor binding sites in these promoter regions, especially the BCL11A repressor site, leads to increased gamma-globin and HbF expression, which is therapeutically beneficial for hemoglobinopathies such as sickle cell disease and beta-thalassemia[1][2][3]. Promoter mutations can also underlie hereditary persistence of fetal hemoglobin (HPFH), a benign condition with high levels of HbF in adulthood[4]. The promoters are a promising therapeutic target for genetic interventions that seek to reactivate fetal hemoglobin production in disease contexts.

Other names

HBG1 promoterHBG2 promoterGamma-globin gene promoterAgamma promoterGgamma promoterHBGA promoterHBGG promoter

Gene editing of the promoter to disrupt binding sites for repressors (e.g., BCL11A) increases fetal hemoglobin (HbF) expression and ameliorates symptoms in sickle cell disease and beta-thalassemia[1][2][3].