Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of the human O6-methylguanine-DNA methyltransferase (MGMT) gene promoter was determined in eight human cell lines by measuring chloramphenicol acetyltransferase activity in a reporter gene system. MGMT promoter activities in cells that do not express MGMT (Mer-) fell within the range of activities seen in cells that do express MGMT (Mer+). The promoter region contains 11 potential binding sites for the transcription factor Sp1, but no correlation was seen between cellular Sp1 protein and MGMT promoter chloramphenicol acetyltransferase activity. Because Mer- cells are not deficient in the factors needed for transcription of MGMT, we suggest that at least two mechanisms regulate MGMT expression. One suppresses MGMT mRNA and protein in Mer- cells, and another regulates the levels of constitutive expression in Mer+ cells. Sp1 is not a limiting factor in MGMT expression.
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PMID:A comparison of human O6-methylguanine-DNA methyltransferase promoter activity in Mer+ and Mer- cells. 142 89

O6-methylguanine-DNA methyltransferase (MGMT) is a ubiquitous protein responsible for repair of O6-alkylguanine, a mutagenic, carcinogenic and toxic lesion. To characterize the elements responsible for the regulation of the MGMT gene, a 2.6 kb Sstl fragment isolated from a genomic clone, was shown to contain 5' flanking sequences of the gene. The promoter activity of this fragment as well as various subfragments were tested in NIH 3T3 mouse fibroblasts by transient expression of the bacterial chloramphenicol acetyltransferase (CAT) gene linked to these fragments. Maximal promoter activity was observed in a 1.2 kb 3' terminal fragment, which contains the first untranslated exon. The transcription initiation site was identified in this fragment by primer extension and S1 mapping. Sequence analysis of this fragment showed the absence of TATA and CAAT boxes but an abundance of extremely GC-rich sequences, including ten GC hexanucleotide motifs 5'CCGCCC. Reduced CAT expression with the minimal promoter sequence suggests the presence of multiple regulatory elements.
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PMID:Characterization of the promoter region of the human O6-methylguanine-DNA methyltransferase gene. 195 75

O6-Methylguanine-DNA methyltransferase plays an important role in cellular defence against mutagens and carcinogens with alkylating activity. Certain tumor-derived cell lines, termed Mer-, are defective in the enzyme activity and have an increased sensitivity to alkylating agents. We cloned the genomic sequence coding for the human O6-methylguanine-DNA methyltransferase and elucidated the structure. The gene consisted of 5 exons and spanned more than 170 kb, while mRNA for the enzyme was 950 nucleotides long. No or only little mRNA for the enzyme was formed in Mer- cells, though there was no gross difference in the coding and promoter regions of the gene between Mer+ and Mer- cells. The putative promoter region, derived from Mer+ cells, was placed upstream of the chloramphenicol acetyltransferase reporter gene and the constructs were introduced into Mer+ and Mer- cells. In Mer- cells, a lowered level of transient expression of the gene was observed as compared with Mer+ cells, but this difference alone does not account for the in vivo difference of expression of the gene in the two types of cells; there might be difference in cis-acting elements. The DNA sequence in the 5' upstream region of the gene was extremely GC-rich and there were no consensus sequences, such as the TATA and CAAT boxes. There were lower levels of methylation in the putative promoter of various Mer- cells, as compared with findings in Mer+ cells. Methylation in this region may be involved in regulating expression of the gene.
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PMID:Organization and expression of the human gene for O6-methylguanine-DNA methyltransferase. 767 40