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Molecular and Cellular Biology, July 2006, p. 4775-4781, Vol. 26, No. 13
0270-7306/06/$08.00+0     doi:10.1128/MCB.00406-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Autonomous Silencing as Well as Competition Controls {gamma}-Globin Gene Expression during Development

Man Yu, Hemei Han, Ping Xiang, Qiliang Li, and George Stamatoyannopoulos*

Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington 98195

Received 8 March 2006/ Returned for modification 6 April 2006/ Accepted 22 April 2006

To investigate the control of the {gamma}-globin gene during development, we produced transgenic mice in which sequences of the ß-gene promoter were replaced by equivalent sequences of the {gamma}-gene promoter in the context of a human ß-globin locus yeast artificial chromosome (ßYAC) and analyzed the effects on globin gene expression during development. Replacement of 1,077 nucleotides (nt) of the ß-gene promoter by 1,359 nt of the {gamma} promoter resulted in striking inhibition of the {gamma}-promoter/ß-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/ß-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 ß genes contributes to the control of {gamma} to ß switching during fetal development.


* Corresponding author. Mailing address: Medical Genetics, Box 357720, University of Washington, Seattle, WA 98195. Phone: (206) 543-3526. Fax: (206) 221-5112. E-mail: gstam{at}u.washington.edu.


Molecular and Cellular Biology, July 2006, p. 4775-4781, Vol. 26, No. 13
0270-7306/06/$08.00+0     doi:10.1128/MCB.00406-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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