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

Abstract

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.

We thank Xin Ye and Mary Stafford for skillful technical help.

This study was supported by National Institutes of Health grants DK61805 and HL73439 to Q.L. and DK45365 to G.S.