Distinct co-regulation of endogenous versus transfected MITF-dependent tyrosinase promoter
Sestáková, B.; Vachtenheim, J.
Folia Biologica 52(5): 161-166
2006
ISSN/ISBN: 0015-5500 PMID: 17116288 Document Number: 603831
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.