Genomic organization and characterization of the promoter region of murine GSTM2 gene.
In this study, we have isolated the genomic clone of the murine GSTM2 gene and determined its sequence. Consistent with the class mu genefamily, the mGSTM2 gene consists of eight exons. The exon-intron boundaries and the distribution of coding sequences within the exons of the known GST class mu family members were found to follow a similar pattern suggesting that various members of this family have originated from a single primordial gene by duplication and the structure has been closely maintained through evolution. By primer extension, the start of transcription was determined to be 40 bp upstream of the initial AUG codon. To gain an understanding of the mGSTM2 regulation, we have also cloned and analyzed its promoter region. Maximal activity was observed in a 170 bp 5'-flanking region. The activity was decreased by 3-fold in a 402 bp 5'-flanking region suggesting the presence of repressor elements. While no TATA box was identified, the presence of an SP1 site at position -38 was noted. Deletion of this SP1 site completely abrogated promoter activity. The promoter contained eight putative Myb responsive elements and its transcriptional activity was upregulated by t-Myb but not by c-Myb.
Kumar
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Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
Reddy
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D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D005796:Genes / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D007438:Introns; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D020598:Proto-Oncogene Proteins c-myb; D011993:Recombinant Fusion Proteins; D004247:DNA; D008156:Luciferases; D005982:Glutathione Transferase; C412602:glutathione S-transferase Mu 2