Autonomous Silencing as Well as Competition Controls γ-Globin Gene Expression during Development

To investigate the control of the γ-globin gene during development, we produced transgenic mice in which sequences of the β-gene promoter were replaced by equivalent sequences of the γ-gene promoter in the context of a human β-globin locus yeast artificial chromosome (βYAC) and analyzed the effects on globin gene expression during development. Replacement of 1,077 nucleotides (nt) of the β-gene promoter by 1,359 nt of the γ promoter resulted in striking inhibition of the γ-promoter/β-gene expression in the adult stage of development, providing direct evidence that the expression of the γ gene in the adult is mainly controlled by autonomous silencing. Measurements of the expression of the γ promoter/β-globin gene as well as the wild γ genes showed that gene competition is also involved in the control of γ-gene expression in the fetal stage of development. We conclude that autonomous silencing is the main mechanism controlling γ-gene expression in the adult, while autonomous silencing as well as competition between γ and β genes contributes to the control of γ to β switching during fetal development.