Hemoglobin subunit gamma 2 promoter regulatory adenines (HBG2 promoter)

The Hemoglobin subunit gamma 2 (HBG2) promoter regulatory adenines are specific nucleotide sequences within the promoter region of the gamma-globin gene that control the transition from fetal to adult hemoglobin production. In healthy adults, these adenine-rich regions are typically bound by transcriptional repressors such as BCL11A and ZBTB7A, which silence HBG2 expression (PubMed: 29072298). Therapeutic strategies, most notably adenine base editing (ABE), target specific adenines at positions such as -175 or -115 relative to the transcription start site to convert them into guanines (Source: Beam Therapeutics). This modification mimics naturally occurring mutations found in individuals with Hereditary Persistence of Fetal Hemoglobin (HPFH), effectively preventing repressor binding or creating new activator sites (PubMed: 33432170). By re-activating the production of fetal hemoglobin, these interventions aim to compensate for the defective or absent beta-globin in patients with sickle cell disease and beta-thalassemia, thereby reducing red blood cell sickling and improving clinical outcomes (PubMed: 32661342).

Other names

HBG2 promoterGamma-globin promoterFetal hemoglobin promoterHBG1/2 promoter regulatory elementsDistal gamma-globin promoter

Induction of fetal hemoglobin (HbF) through adenine base editing (A-to-G conversion) of specific regulatory nucleotides in the HBG2 promoter, which disrupts repressor binding (e.g., BCL11A) or creates de novo activator binding sites to re-activate gamma-globin expression in adults.