title: Fungal mediator tail subunits contain classical transcriptional activation domains.
abstract: Classical activation domains within DNA-bound eukaryotic transcription factors make weak interactions with coactivator complexes, such as Mediator, to stimulate transcription. How these interactions stimulate transcription, however, is unknown. The activation of reporter genes by artificial fusion of Mediator subunits to DNA binding domains that bind to their promoters has been cited as evidence that the primary role of activators is simply to recruit Mediator. We have identified potent classical transcriptional activation domains in the C termini of several tail module subunits of Saccharomyces cerevisiae, Candida albicans, and Candida dubliniensis Mediator, while their N-terminal domains are necessary and sufficient for their incorporation into Mediator but do not possess the ability to activate transcription when fused to a DNA binding domain. This suggests that Mediator fusion proteins actually are functioning in a manner similar to that of a classical DNA-bound activator rather than just recruiting Mediator. Our finding that deletion of the activation domains of S. cerevisiae Med2 and Med3, as well as C. dubliniensis Tlo1 (a Med2 ortholog), impairs the induction of certain genes shows these domains function at native promoters. Activation domains within coactivators are likely an important feature of these complexes and one that may have been uniquely leveraged by a common fungal pathogen.
authors: Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
authors: Zhongle
authors: Z
authors: Liu
authors: Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA larry.myers@dartmouth.edu.
authors: Lawrence C
authors: LC
authors: Myers
mesh_terms: D002175:Candida / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002176:Candida albicans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005686:Galactokinase / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D056892:Mediator Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D015533:Transcriptional Activation
chemical_list: D005656:Fungal Proteins; C470560:MED2 protein, S cerevisiae; D056892:Mediator Complex; C110281:PGD1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; C524219:GAL1 protein, S cerevisiae; D005686:Galactokinase
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