A functional portrait of Med7 and the mediator complex in Candida albicans.
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.
Department of Biology, McGill University, Montreal, Quebec, Canada; Department of Biology, Concordia University, Montreal, Quebec, Canada.
Faiza
F
Tebbji
Department of Biology, Concordia University, Montreal, Quebec, Canada.
Yaolin
Y
Chen
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia Canada.
Julien
J
Richard Albert
Department of Molecular Biology and Microbiology, Tufts University, Boston, Massachusetts, United States of America.
Kearney T W
KT
Gunsalus
Department of Molecular Biology and Microbiology, Tufts University, Boston, Massachusetts, United States of America.
Carol A
CA
Kumamoto
Biotechnology Research Institute, National Research Council, Montreal, Quebec, Canada.
André
A
Nantel
Department of Microbiology-Infectious Disease and Immunology, Laval University, CHU de Québec Research Center (CHUL), Quebec, Quebec, Canada.
Adnane
A
Sellam
Department of Biology, Concordia University, Montreal, Quebec, Canada.
Malcolm
M
Whiteway
D000595:Amino Acid Sequence; D000818:Animals; D002176:Candida albicans / Q000235:genetics* / Q000254:growth & development; D005656:Fungal Proteins / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D025301:Hyphae / Q000235:genetics / Q000254:growth & development; D056892:Mediator Complex / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D046912:Multiprotein Complexes / Q000096:biosynthesis / Q000235:genetics*; D012441:Saccharomyces cerevisiae; D014158:Transcription, Genetic
D005656:Fungal Proteins; D056892:Mediator Complex; D046912:Multiprotein Complexes