Stat3 beta inhibits gamma-globin gene expression in erythroid cells |
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Authors: | Foley Heather A Ofori-Acquah Solomon F Yoshimura Akihiko Critz Stuart Baliga B Surendra Pace Betty S |
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Institution: | Department of Cell Biology and Neuroscience, University of South Alabama, Mobile, Alabama 36688, USA. |
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Abstract: | 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 Stat3 beta 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. |
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