The in vivo expression of the globin genes of theβ cistron in γ-,δ-, andδβ-thalassemia heterozygotes

Abstract

There is considerable evidence suggesting that the switch from γ to δ and β chain production after birth is due, in part, to silencing of the γ genes by stage-specific factors which bind to their promoters and to the competition from the adult (δ and β) genes for a common enhancer element located in the locus control region. As a consequence one can expect that the increased Hb F production in adults with hereditary persistence of fetal hemoglobin or δβ-thalassemia is directed mainly by γ-globin genes in cis to the deletion(s) responsible for these conditions. Here we review data on heterozygotes with γ-, δ-, or δβ-thalassemia, who also had an^Aγ^T mutation, in cis or in trans, which was used as a marker of γ gene expression. The results show that a deletion affecting adult β genes favors the expression of γ genes in cis, while the deletion of a single γ gene does not affect the expression of the β gene in cis but leads to a faster γ→β switch postnatally.