title: GATA transcription factors negatively regulate erythropoietin gene expression.
abstract: We examined regulation of the human erythropoietin (Epo) gene through the GATA sequence in the Epo promoter, and demonstrated that Hep3B and HepG2 cells express human GATA-2 (hGATA-2) mRNA and protein. Nuclear extracts of QT6 cells transfected with hGATA-1, -2 or -3 transcription factors revealed specific binding to the GATA element in the human Epo gene promoter by gel mobility shift assay. Transient transfection of Hep3B cells with hGATA-1, -2 or -3 demonstrated that each of these transcription factors significantly decreased the level of expression of Epo mRNA as assessed by a competitive polymerase chain reaction. Furthermore, transient transfection of Hep3B cells with hGATA-1, -2 and -3 and and Epo reporter gene construct showed significant inhibition of the Epo promoter. We conclude that the hGATA-1, -2 and -3 transcription factors specifically bind to the GATA element in the human Epo gene promoter and negatively regulate Epo gene expression.
authors.affiliation: Department of Medicine, Jichi Medical School, Tochigi-ken, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Imagawa
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Miura
mesh_terms: D000693:Anaerobiosis; D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D004921:Erythropoietin / Q000096:biosynthesis / Q000235:genetics*; D050989:GATA2 Transcription Factor; D005786:Gene Expression Regulation / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D004921:Erythropoietin