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 journalArticle

23 Citations (Scopus)

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
Pages (from-to)16211-16219
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number18
DOIs
Publication statusPublished - 2002 May 3
Externally publishedYes

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Erythroid Cells
Globins
Gene expression
Gene Expression
Genes
Gene Silencing
Interleukin-6
Signal transduction
Phosphorylation
K562 Cells
5' Untranslated Regions
DNA-Binding Proteins
Genetic Promoter Regions
Transfection
Signal Transduction
Binding Sites
Cytokines
Experiments

ASJC Scopus subject areas

  • Biochemistry

Cite this

Foley, H. A., Ofori-Acquah, S. F., Yoshimura, A., Critz, S., Surendra Baliga, B., & Pace, B. S. (2002). Stat3β inhibits γ-globin gene expression in erythroid cells. Journal of Biological Chemistry, 277(18), 16211-16219. https://doi.org/10.1074/jbc.M106556200

Stat3β inhibits γ-globin gene expression in erythroid cells. / Foley, Heather A.; Ofori-Acquah, Solomon F.; Yoshimura, Akihiko; Critz, Stuart; Surendra Baliga, B.; Pace, Betty S.

In: Journal of Biological Chemistry, Vol. 277, No. 18, 03.05.2002, p. 16211-16219.

Research output: Contribution to journalArticle

Foley, HA, Ofori-Acquah, SF, Yoshimura, A, Critz, S, Surendra Baliga, B & Pace, BS 2002, 'Stat3β inhibits γ-globin gene expression in erythroid cells', Journal of Biological Chemistry, vol. 277, no. 18, pp. 16211-16219. https://doi.org/10.1074/jbc.M106556200
Foley HA, Ofori-Acquah SF, Yoshimura A, Critz S, Surendra Baliga B, Pace BS. Stat3β inhibits γ-globin gene expression in erythroid cells. Journal of Biological Chemistry. 2002 May 3;277(18):16211-16219. https://doi.org/10.1074/jbc.M106556200
Foley, Heather A. ; Ofori-Acquah, Solomon F. ; Yoshimura, Akihiko ; Critz, Stuart ; Surendra Baliga, B. ; Pace, Betty S. / Stat3β inhibits γ-globin gene expression in erythroid cells. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 18. pp. 16211-16219.
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