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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
Stat3 Inhibits -Globin Gene Expression in Erythroid
Cells*
Heather A.
Foley ,
Solomon F.
Ofori-Acquah ,
Akihiko
Yoshimura§,
Stuart
Critz ,
B. Surendra
Baliga¶, and
Betty
S.
Pace ¶
From the 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 -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 gene silencing in erythroid cells.
DNA-protein binding studies established Stat3 interaction in the
5'-untranslated -globin promoter region. Furthermore,
co-transfection experiments with Stat3 demonstrate 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 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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