title: Cis-elements in the promoter region of the human myeloperoxidase (MPO) gene.
abstract: We recently reported the identification and initial characterization of the human myeloperoxidase (MPO) promoter. The minimal or basic MPO promoter lies within the proximal 128 bp of the 5'-flanking region of the MPO gene. Plasmids containing progressively larger segments of the 5'-flanking region show correspondingly greater MPO promoter activity and increased tissue specificity compared with smaller promoter fragments. These findings suggested the presence of a multiple important regulatory cis-elements in the 5'-flanking region of the MPO gene. We now report results of studies which reveal the presence of seven discrete nuclear protein binding sites (DP1-DP7) within the proximal 600 bp of 5'-flanking MPO DNA. DNase I footprinting and gel shift analyses indicate tissue-specific and/or maturation-specific differences in nuclear protein binding to most of these sites, suggesting that they play a role in transcriptional regulation. Mutation of site DP7 stimulates the activity of a 594-bp MPO promoter construct in transfection studies, whereas mutation of any of the six other sites (DP1-DP6) reduces promoter activity. These results indicate that oligonucleotides DP1-DP7 constitute cis-elements which contribute to the activity of the human MPO promoter.
authors.affiliation: Department of Pathology, Veterans Affairs Medical Center, Decatur, GA 30033, USA.
authors.forename: W G
authors.initials: WG
authors.lastname: Zhao
authors.forename: A
authors.initials: A
authors.lastname: Regmi
authors.forename: E D
authors.initials: ED
authors.lastname: Austin
authors.forename: J E
authors.initials: JE
authors.lastname: Braun
authors.forename: M
authors.initials: M
authors.lastname: Racine
authors.forename: G E
authors.initials: GE
authors.lastname: Austin
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D018983:DNA Footprinting; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D009841:Oligonucleotides / Q000235:genetics; D009195:Peroxidase / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014162:Transfection
chemical_list: D009687:Nuclear Proteins; D009841:Oligonucleotides; D009195:Peroxidase