Role of STAT3 and GATA-1 interactions in gamma-globin gene expression.
Role of STAT3 and GATA-1 interactions in gamma-globin gene expression.
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DOI：
10.1016/j.exphem.2009.05.004
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发表时间：
2009-08
影响因子：
2.6
通讯作者：
Pace, Betty S.
中科院分区：
文献类型：
--
作者：
Yao, Xiao;Kodeboyina, Sirisha;Liu, Li;Dzandu, James;Sangerman, Jose;Ofori-Acquah, Solomon F.;Pace, Betty S.
We previously demonstrated a silencing role for Stat3 in γ-globin gene regulation in primary erythroid cells. Recently GATA-1, a key transcription factor involved in hematopoietic cell development was shown to directly inhibit the activity of Stat3 in vivo. Therefore we completed studies to determine if interactions between these two factors influence γ-globin gene expression. Chromatin immunoprecipitation (ChIP) assay was used to ascertain in vivo protein binding at the γ-globin 5’untranslated region (5’UTR); protein-protein interactions were examined by co-immunoprecipitation analysis. In vitro protein-DNA binding were completed using surface plasmon resonance and electrophoretic mobility shift assay (EMSA). Activity of a luciferase γ-globin promoter reporter, and levels of γ-globin mRNA and fetal hemoglobin in stable K562 cell lines over-expressing Stat3 and GATA-1 were used to determine the influence of the Stat3/GATA-1 interaction on γ-globin gene expression. We observed interaction between Stat3 and GATA-1 in K562 and mouse erythroleukemia cells in vivo at the γ-globin 5’UTR by ChIP assay. EMSA performed with a 41 base pair DNA probe (γ41) demonstrated the presence of Stat3 and GATA-1 proteins in complexes assembled at the γ-globin 5’UTR. A consensus Stat3 binding DNA probe inhibited GATA-1 binding in a concentration-dependent manner, and the converse was also true. Enforced Stat3 expression augmented its binding at the γ-globin 5’UTR in vivo and silenced γ-promoter driven luciferase activity. Stable enforced Stat3 expression in K562 cells reduced endogenous γ-globin mRNA level. This effect was reversed by GATA-1. These data provide evidence that GATA-1 can reverse Stat3-mediated γ-globin gene silencing in erythroid cells.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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DOI：
10.1016/0002-9378(76)90812-7
发表时间：
1976-01-01
影响因子：
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作者：
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通讯作者：
WISER, WL