Distinct co-regulation of endogenous versus transfected MITF-dependent tyrosinase promoter.
The tissue-specific control of gene activation in melanocytes is directed by the microphthalmia-associated transcription factor (MITF), a master regulator of melanocyte development and differentiation. Tyrosinase is a rate-limiting enzyme in melanin biosynthesis and a prototypic MITF target. While the expression of tyrosinase is restricted to pigmented cells, the transfected tyrosinase promoter is active in a broad range of cell types if ectopic MITF is co-expressed. Here we used the E1A oncoprotein and its mutants as repressors of both the transiently transfected and endogenous tyrosinase promoter. We report that the requirement of the E1A N-terminus for repression of the MITF-activated tyrosinase promoter and the sensitivity to derepression by the histone deacetylase inhibitor trichostatin A are distinct when the activity of the transiently transfected or the endogenous promoter is analysed in U2-OS cells. Thus, for transiently transfected versus chromatin-embedded promoter, the activity of obligatory MITF seems to be executed through different mechanisms of transcriptional coactivation.
Sestáková
B
B
Laboratory of Molecular Biology, University Hospital, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic.
Vachtenheim
J
J
D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D011518:Proto-Oncogene Proteins; C012589:trichostatin A; D014442:Monophenol Monooxygenase