Drosophila Med6 Is Required for Elevated Expression of a Large but Distinct Set of Developmentally Regulated Genes

Abstract

Mediator is the evolutionarily conserved coactivator required for the integration and recruitment of diverse regulatory signals to basal transcription machinery. To elucidate the functions of metazoan Mediator, we isolated Drosophila melanogaster Med6mutants. dMed6 is essential for viability and/or proliferation of most cells. dMed6 mutants failed to pupate and died in the third larval instar with severe proliferation defects in imaginal discs and other larval mitotic cells. cDNA microarray, quantitative reverse transcription-PCR, and in situ expression analyses of developmentally regulated genes in dMed6 mutants showed that transcriptional activation of many, but not all, genes was affected. Among the genes found to be affected were some that play a role in cell proliferation and metabolism. Therefore, dMed6 is required in most cells for transcriptional regulation of many genes important for diverse aspects of Drosophila development.

ACKNOWLEDGMENTS

We thank Jeongsil Kim-Ha for expert assistance. We thank Juri Kim for assistance to isolate dMed6 mutants. We thank Thomas Kaufman, Michael Levine, Ulrich Nauber, Todd Laverty, Kei Ito, Carl Hashimoto, Marcelo Jacobs-Lorena, Judith Lengyel, Michael Weir, Carl Thummel, and the Bloomington and Umea stock centers for kindly providing plasmids and fly stocks. We are grateful to John T. Lis and Bruce Baker for critical reading and comments.

This work was supported by a Creative Research Initiatives (CRI) grant from the Ministry of Science and Technology, Korea, to Y.-J.K. and the Brain Korea 21 Project to C.K.