MBP-1 physically associates with histone deacetylase for transcriptional repression.
MBP-1, a c-myc promoter binding protein, is a mammalian transcription factor with intriguing properties including transcriptional repression of cellular genes. Recently, we have identified and characterized two different repressor domains of MBP-1. In this report, we have demonstrated that MBP-1 physically associates with histone deacetylase (HDAC), thus promoting formation of neucleosomes that inhibit transcription. Trichostatin A, an inhibitor of histone deacetylase, significantly reduces MBP-1-mediated transcriptional repression. However, MBP-1-mediated repression on c-myc promoter is resistant to histone deacetylase activity. Our results suggest that MBP-1 represses transcription by recruiting histone deacetylase as one of the mechanisms, whereas the other mechanism is resistant to HDAC activity and probably related to direct binding of promoter sequences or interaction through yet unidentified factor.
Department of Pathology, Saint Louis University, St. Louis, Missouri, 63104, USA.
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D016475:3T3 Cells; D000818:Animals; D014408:Biomarkers, Tumor; D002460:Cell Line; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016259:Genes, myc; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; C012589:trichostatin A; D006655:Histone Deacetylases; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase