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Originally published In Press as doi:10.1074/jbc.M106556200 on February 20, 2002

J. Biol. Chem., Vol. 277, Issue 18, 16211-16219, May 3, 2002
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Stat3beta Inhibits gamma -Globin Gene Expression in Erythroid Cells*

Heather A. FoleyDagger , Solomon F. Ofori-AcquahDagger , Akihiko Yoshimura§, Stuart CritzDagger , B. Surendra Baliga, and Betty S. PaceDagger ||

From the Dagger  Department of Cell Biology and Neuroscience, University of South Alabama, Mobile, Alabama 36688, the § Department of Molecular and Cellular Immunology, Kyushu University, Fukuoka, Japan, and the  Department of Pediatrics, University of South Alabama, Mobile, Alabama 36606

We demonstrated previously gamma -globin gene inhibition in K562 cells and primary erythroid progenitors treated with interleukin-6. Although several cis-acting elements have been identified in the globin promoters, the precise mechanism for cytokine-mediated globin gene regulation remains to be elucidated. In this report we demonstrate inhibitors of Stat3 phosphorylation abrogate interleukin-6-mediated gamma  gene silencing in erythroid cells. DNA-protein binding studies established Stat3 interaction in the 5'-untranslated gamma -globin promoter region. Furthermore, co-transfection experiments with Stat3beta demonstrate gamma  promoter inhibition in a concentration-dependent manner, which was significantly reversed when the cognate Stat3-binding site in the 5'-untranslated region was mutated. These studies establish a novel mechanism for gamma  gene silencing through the STAT signal transduction pathway.


* This work was supported by National Institutes of Health Grant HL 38639 (to B. S. P.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

|| To whom correspondence should be addressed: Dept. of Cell Biology and Neuroscience, University of South Alabama, 307 University Blvd., MSB 2406, Mobile, AL 36688. Tel.: 334-460-6109; Fax: 334-460-6771; E-mail: bpace@usouthal.edu.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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