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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Cell Line, Tumor, DNA Modification Methylases, DNA Repair, DNA Repair Enzymes, Gene Expression Regulation, Neoplastic, Haplotypes, Humans, Promoter Regions, Genetic, Protein Binding, Transcription Factors, Transcription, Genetic, Tumor Suppressor Proteins.
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Do mGMT DNA repair gene promoter/enhancer haplotypes alter transcription factor binding and gene expression? Context: The O In this study, we test the hypothesis that MGMT P/E haplotypes affect MGMT promoter activity by altering transcription factor (TF) binding to the P/E region. We used a promoter binding TF profiling array and a reporter assay to evaluate the effect of different P/E haplotypes on TF binding and MGMT expression, respectively. Our data revealed a significant difference in TF binding profiles between the different haplotypes evaluated. We identified TFs that consistently showed significant haplotype-dependent binding alterations (p ≤ 0.01) and revealed their role in regulating MGMT expression using siRNAs and a dual-luciferase reporter assay system.
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The data generated support our hypothesis that promoter haplotypes alter the binding of TFs to the MGMT P/E and, subsequently, affect their regulatory function on MGMT promoter activity and expression level. Final Decision: yes