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A functional portrait of Med7 and the mediator complex in Candida albicans.

PLoS genetics | 2014

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.

Pubmed ID: 25375174 RIS Download

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: GM074869
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI081794
  • Agency: Canadian Institutes of Health Research, Canada
    Id: MOP-42516
  • Agency: NIGMS NIH HHS, United States
    Id: K12 GM074869
  • Agency: NIAID NIH HHS, United States
    Id: R56 AI081794
  • Agency: Canadian Institutes of Health Research, Canada
    Id: 42516-4
  • Agency: NIAID NIH HHS, United States
    Id: AI081794

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This is a list of tools and resources that we have found mentioned in this publication.


Candida Genome Database (tool)

RRID:SCR_002036

Database of genetic and molecular biological information about Candida albicans. Contains information about genes and proteins, descriptions and classifications of their biological roles, molecular functions, and subcellular localizations, gene, protein, and chromosome sequence information, tools for analysis and comparison of sequences and links to literature information. Each CGD gene or open reading frame has an individual Locus Page. Genetic loci that are not tied to DNA sequence also have Locus Pages. Provides Gene Ontology, GO, to all its users. Three ontologies that comprise GO (Molecular Function, Cellular Component, and Biological Process) are used by multiple databases to annotate gene products, so that this common vocabulary can be used to compare gene products across species. Development of ontologies is ongoing in order to incorporate new information. Data submissions are welcome.

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Gene Set Enrichment Analysis (tool)

RRID:SCR_003199

Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.

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SGD (tool)

RRID:SCR_004694

A curated database that provides comprehensive integrated biological information for Saccharomyces cerevisiae along with search and analysis tools to explore these data. SGD allows researchers to discover functional relationships between sequence and gene products in fungi and higher organisms. The SGD also maintains the S. cerevisiae Gene Name Registry, a complete list of all gene names used in S. cerevisiae which includes a set of general guidelines to gene naming. Protein Page provides basic protein information calculated from the predicted sequence and contains links to a variety of secondary structure and tertiary structure resources. Yeast Biochemical Pathways allows users to view and search for biochemical reactions and pathways that occur in S. cerevisiae as well as map expression data onto the biochemical pathways. Literature citations are provided where available.

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Biological General Repository for Interaction Datasets (BioGRID) (tool)

RRID:SCR_007393

Curated protein-protein and genetic interaction repository of raw protein and genetic interactions from major model organism species, with data compiled through comprehensive curation efforts.

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GenScript (tool)

RRID:SCR_002891

Commercial organization which provides life science services and products to researchers. They specialize in gene synthesis, peptide, protein, antibody and preclinical drug development service.

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Swiss Webster (tool)

RRID:MGI:2160840

laboratory mouse with name Swiss Webster from MGI.

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