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Molecular and Cellular Biology, September 2006, p. 6832-6843, Vol. 26, No. 18
0270-7306/06/$08.00+0     doi:10.1128/MCB.01770-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Antagonistic Regulation of ß-Globin Gene Expression by Helix-Loop-Helix Proteins USF and TFII-I

Valerie J. Crusselle-Davis, Karen F. Vieira, Zhuo Zhou, Archana Anantharaman, and Jörg Bungert*

Department of Biochemistry and Molecular Biology, Powell Gene Therapy Center, Center for Mammalian Genetics, and Genetics Institute, University of Florida, Gainesville, Florida 32610

Received 8 September 2005/ Returned for modification 8 October 2005/ Accepted 26 June 2006

The human ß-globin genes are expressed in a developmental stage-specific manner in erythroid cells. Gene-proximal cis-regulatory DNA elements and interacting proteins restrict the expression of the genes to the embryonic, fetal, or adult stage of erythropoiesis. In addition, the relative order of the genes with respect to the locus control region contributes to the temporal regulation of the genes. We have previously shown that transcription factors TFII-I and USF interact with the ß-globin promoter in erythroid cells. Herein we demonstrate that reducing the activity of USF decreased ß-globin gene expression, while diminishing TFII-I activity increased ß-globin gene expression in erythroid cell lines. Furthermore, a reduction of USF activity resulted in a significant decrease in acetylated H3, RNA polymerase II, and cofactor recruitment to the locus control region and to the adult ß-globin gene. The data suggest that TFII-I and USF regulate chromatin structure accessibility and recruitment of transcription complexes in the ß-globin gene locus and play important roles in restricting ß-globin gene expression to the adult stage of erythropoiesis.

* Corresponding author. Mailing address: Department of Biochemistry, and Molecular Biology, College of Medicine, University of Florida, P.O. Box 100245, 1600 SW Archer Road, Gainesville, FL 32610. Phone: (352) 392-0121. Fax: (352) 392-2953. E-mail: jbungert{at}ufl.edu.

Molecular and Cellular Biology, September 2006, p. 6832-6843, Vol. 26, No. 18
0270-7306/06/$08.00+0     doi:10.1128/MCB.01770-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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