Metazoan transcriptional Mediator complex as the integrator of Gene-specific transcriptional regulation signals

다국어 초록 (Multilingual Abstract)

The Mediator complex is generally required for transcriptional regulation in species ranging from yeast to human. Throughout evolution, the functional diversity of the Mediator complex has been enhanced to meet the increasing requirement for sophisticated gene regulation. We took systematic biochemical and genomics approaches to examine various types of Mediator proteins in Drosophila melanogaster. Such efforts led to the identification of three distinct forms of Mediator complexes. In exploring their compositional and functional heterogeneity, we found that different cell types may require distinct Mediator complexes, some of which may participate in nuclear processes other than the previously identified functions. On the top of the complex heterogeneity, several Mediator genes show distinct mutant phenotype thus were suggested to mediate transcriptional regulation of distinct group of genes via activator-specific interactions. However, their physiological relevance and activator-specificities in cell have not been addressed. Using biochemical analysis coupled with RNAi-mutational analysis, we confirmed that physical interaction between specific activator proteins and dTRAP80 is required for transcriptional activation of distinct group of genes in vivo. We extended this study to other Mediator genes by generating mutant Mediator cells and examining their defect on transcriptional regulation with the use of micro array analysis.