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The Mediator subunit MDT-15 confers metabolic adaptation to ingested material.

Taubert, Stefan and Hansen, Malene and Van Gilst, Marc R and Cooper, Samantha B and Yamamoto, Keith R (2008) The Mediator subunit MDT-15 confers metabolic adaptation to ingested material. PLoS genetics, 4 (2). e1000021. ISSN 1553-7404

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In eukaryotes, RNA polymerase II (Pol(II)) dependent gene expression requires accessory factors termed transcriptional coregulators. One coregulator that universally contributes to Pol(II)-dependent transcription is the Mediator, a multisubunit complex that is targeted by many transcriptional regulatory factors. For example, the Caenorhabditis elegans Mediator subunit MDT-15 confers the regulatory actions of the sterol response element binding protein SBP-1 and the nuclear hormone receptor NHR-49 on fatty acid metabolism. Here, we demonstrate that MDT-15 displays a broader spectrum of activities, and that it integrates metabolic responses to materials ingested by C. elegans. Depletion of MDT-15 protein or mutation of the mdt-15 gene abrogated induction of specific detoxification genes in response to certain xenobiotics or heavy metals, rendering these animals hypersensitive to toxin exposure. Intriguingly, MDT-15 appeared to selectively affect stress responses related to ingestion, as MDT-15 functional defects did not abrogate other stress responses, e.g., thermotolerance. Together with our previous finding that MDT-15:NHR-49 regulatory complexes coordinate a sector of the fasting response, we propose a model whereby MDT-15 integrates several transcriptional regulatory pathways to monitor both the availability and quality of ingested materials, including nutrients and xenobiotic compounds.

Item Type: Article or Abstract
DOI: 10.1371/journal.pgen.1000021
PubMed ID: 18454197
PMCID: PMC2265483
Grant Numbers: 5R01CA020535-29, E07139, E5191
Keywords or MeSH Headings: Adaptation, Physiological; Animals; Caenorhabditis elegans/drug effects/genetics/metabolism; Caenorhabditis elegans Proteins/antagonists & inhibitors/chemistry/genetics/metabolism; Food; Gene Expression Profiling; Genes, Helminth; Heat-Shock Response/genetics/physiology; Lipid Metabolism; Metabolic Detoxication, Drug; Metals, Heavy/metabolism/toxicity; Models, Biological; Mutation; Protein Subunits; RNA Interference; Trans-Activators/antagonists & inhibitors/chemistry/genetics/metabolism; Xenobiotics/metabolism/toxicity;
Subjects: Molecules > Proteins > Transcription factors
Cellular and Organismal Processes > Metabolism
Cellular and Organismal Processes > Genetic processes > Transcription
Depositing User: Library Staff
Date Deposited: 30 Sep 2008 21:08
Last Modified: 08 May 2010 00:21

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