Fetal hemoglobin gene expression (specifically, regulation of the gamma-globin gene) (HbF gene expression (or γ-globin gene expression))

Fetal hemoglobin gene expression describes the activation of γ-globin genes (*HBG1* and *HBG2*) resulting in fetal hemoglobin (HbF, α₂γ₂) production during fetal development. Normally, γ-globin expression is silenced postnatally in favor of adult β-globin. Persistent or reactivated fetal hemoglobin suppresses the pathological manifestations of sickle cell disease and β-thalassemia. Regulation involves transcription factors (notably BCL11A, KLF1, LRF), epigenetic mechanisms (DNA methylation, histone modifications), and cellular signaling pathways, such as the sGC–PKG pathway. Several drugs, notably hydroxyurea, and emerging gene therapies target these regulatory processes to therapeutically elevate HbF levels in patients with hemoglobinopathies[1][2][3][4][5][6].

Other names

HbF regulationGamma-globin gene expressionFetal globin gene expressionHBG1/HBG2 expression

Transcriptional activation of γ-globin genes Inhibition of HbF repressors (e.g., BCL11A) Activation of signal transduction pathways (e.g., sGC–PKG pathway)