The murine myeloperoxidase promoter contains several functional elements, one of which binds a cell type-restricted transcription factor, myeloid nuclear factor 1 (MyNF1).
The myeloperoxidase (MPO) gene is expressed specifically in myeloid cells. There is significant homology between the murine and human MPO genes in the 1.6-kb region located upstream of the murine MPO transcription initiation sites. 5',3', and internal deletions of this DNA segment localized several cis-acting DNA elements in the murine MPO promoter which are functional in 32D cl3 cells, a murine myeloblast cell line which expresses MPO. These DNA elements did not function well in mouse L-cell fibroblasts. Additional mutagenesis of the most active promoter region allowed the delimitation of a functional 20-bp segment. Mutation of the enhancer core motif within this segment was functionally deleterious, and an oligonucleotide containing these base pairs increased the activity of a minimal promoter. This same oligonucleotide, but not a mutant variant, could bind a set of nuclear proteins, myeloid nuclear factors 1 alpha and 1 beta (MyNF1 alpha and -1 beta), present in 32D cl3 cells but absent from L cells, murine erythroleukemia cells, and SP2 lymphoid cells.
Division of Pediatric Oncology, Johns Hopkins Oncology Center, Johns Hopkins University, Baltimore, Maryland 21287.
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Suzow
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Friedman
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D009195:Peroxidase / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D004268:DNA-Binding Proteins; C080323:Mynf1 protein, mouse; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D014157:Transcription Factors; D009195:Peroxidase