1. Autonomous Silencing as Well as Competition Controls γ-Globin Gene Expression during Development
- Author
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Hemei Han, Qiliang Li, George Stamatoyannopoulos, Man Yu, and Ping Xiang
- Subjects
chemistry.chemical_classification ,Yeast artificial chromosome ,Genetically modified mouse ,Fetus ,Gene Expression Regulation, Developmental ,Mice, Transgenic ,Locus (genetics) ,Articles ,Cell Biology ,Biology ,Embryo, Mammalian ,Molecular biology ,Globins ,Fetal Development ,Mice ,chemistry ,Gene expression ,Animals ,Gene silencing ,Erythropoiesis ,Nucleotide ,Gene Silencing ,Promoter Regions, Genetic ,Molecular Biology ,Gene - Abstract
To investigate the control of the gamma-globin gene during development, we produced transgenic mice in which sequences of the beta-gene promoter were replaced by equivalent sequences of the gamma-gene promoter in the context of a human beta-globin locus yeast artificial chromosome (betaYAC) and analyzed the effects on globin gene expression during development. Replacement of 1,077 nucleotides (nt) of the beta-gene promoter by 1,359 nt of the gamma promoter resulted in striking inhibition of the gamma-promoter/beta-gene expression in the adult stage of development, providing direct evidence that the expression of the gamma gene in the adult is mainly controlled by autonomous silencing. Measurements of the expression of the gamma promoter/beta-globin gene as well as the wild gamma genes showed that gene competition is also involved in the control of gamma-gene expression in the fetal stage of development. We conclude that autonomous silencing is the main mechanism controlling gamma-gene expression in the adult, while autonomous silencing as well as competition between gamma and beta genes contributes to the control of gamma to beta switching during fetal development.
- Published
- 2006
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