Journal article
Differential Roles of Transcriptional Mediator Subunits in Regulation of Multidrug Resistance Gene Expression in Saccharomyces cerevisiae
Molecular biology of the cell, Vol.21(14), pp.2469-2482
07/15/2010
DOI: 10.1091/mbc.E09-10-0899
PMCID: PMC2903675
PMID: 20505076
Abstract
Med12 is a transcriptional Mediator subunit most typically associated with negative control of gene expression. Here Med12 is demonstrated to serve as a positive regulator required for activation of multidrug resistance gene expression in yeast cells lacking their mitochondrial genome.
The multiprotein transcriptional Mediator complex provides a key link between RNA polymerase II and upstream transcriptional activator proteins. Previous work has established that the multidrug resistance transcription factors Pdr1 and Pdr3 interact with the Mediator component Med15/Gal11 to drive normal levels of expression of the ATP-binding cassette transporter-encoding gene
PDR5
in
Saccharomyces cerevisiae. PDR5
transcription is induced upon loss of the mitochondrial genome (ρ
0
cells) and here we provide evidence that this ρ
0
induction is Med15 independent. A search through other known Mediator components determined that Med12/Srb8, a member of the CDK8 Mediator submodule, is required for ρ
0
activation of
PDR5
transcription. The CDK8 submodule contains the cyclin C homologue (CycC/Srb11), cyclin-dependent kinase Cdk8/Srb10, and the large Med13/Srb9 protein. Loss of these other proteins did not lead to the same block in
PDR5
induction. Chromatin immunoprecipitation analyses demonstrated that Med15 is associated with the
PDR5
promoter in both ρ
+
and ρ
0
, whereas Med12 recruitment to this target promoter is highly responsive to loss of the mitochondrial genome. Coimmunoprecipitation experiments revealed that association of Pdr3 with Med12 can only be detected in ρ
0
cells. These experiments uncover the unique importance of Med12 in activated transcription of
PDR5
seen in ρ
0
cells.
Details
- Title: Subtitle
- Differential Roles of Transcriptional Mediator Subunits in Regulation of Multidrug Resistance Gene Expression in Saccharomyces cerevisiae
- Creators
- Puja Shahi - Roy J. and Lucille A. Carver College of MedicineKailash Gulshan - Roy J. and Lucille A. Carver College of MedicineAnders M. Näär - Massachusetts General HospitalW. Scott Moye-Rowley - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Molecular biology of the cell, Vol.21(14), pp.2469-2482
- Publisher
- The American Society for Cell Biology
- DOI
- 10.1091/mbc.E09-10-0899
- PMID
- 20505076
- PMCID
- PMC2903675
- ISSN
- 1059-1524
- eISSN
- 1939-4586
- Language
- English
- Date published
- 07/15/2010
- Academic Unit
- Molecular Physiology and Biophysics; Internal Medicine
- Record Identifier
- 9984297501102771
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