Stat3β inhibits γ-globin gene expression in erythroid cells

Heather A. Foley, Solomon F. Ofori-Acquah, Akihiko Yoshimura, Stuart Critz, B. Surendra Baliga, Betty S. Pace

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

We demonstrated previously γ-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 γ gene silencing in erythroid cells. DNA-protein binding studies established Stat3 interaction in the 5′-untranslated γ-globin promoter region. Furthermore, co-transfection experiments with Stat3β demonstrate γ 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 γ gene silencing through the STAT signal transduction pathway.

Original languageEnglish (US)
Pages (from-to)16211-16219
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number18
DOIs
StatePublished - May 3 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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