Regulation of gamma globin expression and fetal hemoglobin levels

The switch from Hb F to Hb A occurs shortly after birth. The degree of Hb F expression is a quantitative trait with multiple influences; the main quantitative trait loci (QTL) are the genes BCL11A and the HBS1L-MYB intergenic region (HMIP), which encode transcription factors, and the Xmn1 polymorphism in the HBG2 promoter.

Hemoglobin switching is the result of developmentally timed inactivation and activation of genes within the HBB cluster that influence expression of gamma globin from the HBG2 and HBG1 genes, in turn affecting Hb F levels.

Transcription factors involved in nuclear chromatin remodeling (NuRD) complexes affect ZBTBT7A and BCL11A, along with genetic and epigenetic regulators, and control gamma globin production.