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

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)376-381
Number of pages6
JournalInternational journal of hematology
Volume75
Issue number4
DOIs
Publication statusPublished - 2002 May
Externally publishedYes

Keywords

  • Erythropoietin
  • GATA
  • HO
  • L-NMMA
  • Transcriptional regulation

ASJC Scopus subject areas

  • Hematology

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