GATA suppresses erythropoietin gene expression through GATA site in mouse erythropoietin gene promoter

Shigehiko Imagawa, Norio Suzuki, Ken Ohmine, Naoshi Obara, Harumi Y. Mukai, Keiya Ozawa, Masayuki Yamamoto, Toshiro Nagasawa

研究成果: Article査読

21 被引用数 (Scopus)

抄録

The promoter and enhancer elements of the mouse erythropoietin (mEpo) gene, which have high homology with those of the human erythropoietin (hEpo) gene, were fused with luciferase. The construct was transfected into erythropoietin-producing hepatoma cell line (Hep3B) cells by lipofectin with lacZ as an internal standard. The wild type (TGATA) showed a 39.5-fold increase in induction by hypoxia. Mouse GATA-2 inhibited the hypoxic induction of the wild-type (m3), promoter-luciferase construct but not the hypoxic induction of the mutant (m4, 5) promoter-luciferase constructs. NG-monomethyl L-arginine (L-NMMA) inhibited the hypoxic induction of the m3 promoter-luciferase construct, but this inhibition was recovered by L-arginine. H2O2 also inhibited the hypoxic induction of the m3 promoter-luciferase construct, but this inhibition was recovered by catalase. Gel shift assays performed on nuclear extracts of 293 cells overexpressing mGATA-1, -2, and -3 revealed that mGATA-1, -2, and -3 bind to the TGATA element of the mEpo promoter. These results indicate that mGATA binds to the TGATA site of the mEpo promoter and negatively regulates mEpo gene expression. Negative regulation of mEpo gene by GATA transcriptional factors is discussed.

本文言語English
ページ(範囲)376-381
ページ数6
ジャーナルInternational journal of hematology
75
4
DOI
出版ステータスPublished - 2002 5月
外部発表はい

ASJC Scopus subject areas

  • 血液学

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