Journal Article

A Functional Portrait of Med7 and the Mediator Complex in Candida albicans

Chen, Yaolin, Nantel, André, Department of Medical Genetics, University of British Columbia, Faculty of Medicine, Department of Microbiology and Immunology, Laval University, Canada, Kumamoto, Carol, Sellam, Adnane, Whiteway, Malcolm, Department of Biology at Concordia University, Gunsalus, Kearney, Department of Biology [McGill University] ; McGill University = Université McGill [Montréal, Canada], Tebbji, Faiza, Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America, BIOTECHNOLOGY RESEARCH INSTITUTE NATIONAL RESEARCH COUNCIL OF CANADA MONTREAL CAN ; Partenaires IRSTEA ; Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Richard Albert, Julien

2014

Overview

Mediator is a multi-subunit protein complex that regulates gene expression in eukaryotes by integrating physiological and developmental signals and transmitting them to the general RNA polymerase II machinery. We examined, in the fungal pathogen Candida albicans, a set of conditional alleles of genes encoding Mediator subunits of the head, middle, and tail modules that were found to be essential in the related ascomycete Saccharomyces cerevisiae. Intriguingly, while the Med4, 8, 10, 11, 14, 17, 21 and 22 subunits were essential in both fungi, the structurally highly conserved Med7 subunit was apparently non-essential in C. albicans. While loss of CaMed7 did not lead to loss of viability under normal growth conditions, it dramatically influenced the pathogen's ability to grow in different carbon sources, to form hyphae and biofilms, and to colonize the gastrointestinal tracts of mice. We used epitope tagging and location profiling of the Med7 subunit to examine the distribution of the DNA sites bound by Mediator during growth in either the yeast or the hyphal form, two distinct morphologies characterized by different transcription profiles. We observed a core set of 200 genes bound by Med7 under both conditions; this core set is expanded moderately during yeast growth, but is expanded considerably during hyphal growth, supporting the idea that Mediator binding correlates with changes in transcriptional activity and that this binding is condition specific. Med7 bound not only in the promoter regions of active genes but also within coding regions and at the 3' ends of genes. By combining genome-wide location profiling, expression analyses and phenotyping, we have identified different Med7p-influenced regulons including genes related to glycolysis and the Filamentous Growth Regulator family. In the absence of Med7, the ribosomal regulon is de-repressed, suggesting Med7 is involved in central aspects of growth control.

• Publisher: HAL CCSD,Public Library of Science,Public Library of Science (PLoS)
• Subject: Allelomorphism / Amino Acid Sequence / Animals / Biofilms / Biology and Life Sciences / Candida albicans / Candida albicans - genetics / Candida albicans - growth & development / Carbon / Deoxyribonucleic acid / DNA / Fungal Proteins - genetics / Gene expression / Gene Expression Regulation, Fungal / Genetic aspects / Genomes / Hyphae - genetics / Hyphae - growth & development / Kinases / Life Sciences / Mediator Complex - biosynthesis / Mediator Complex - genetics / Mice / Microbiological research / Multiprotein Complexes - biosynthesis / Multiprotein Complexes - genetics / Physiological aspects / Protein research / Proteins / RNA polymerases / Saccharomyces cerevisiae / Transcription, Genetic / Yeast