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

• Published in: PLoS genetics Vol. 4; no. 2; p. e1000021
• Main Authors: Taubert, Stefan, Hansen, Malene, Van Gilst, Marc R, Cooper, Samantha B, Yamamoto, Keith R
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.02.2008; Public Library of Science (PLoS)
• Subjects: Adaptation, Physiological; Animals; Caenorhabditis elegans - drug effects; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - antagonists & inhibitors; Caenorhabditis elegans Proteins - chemistry; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell Biology/Gene Expression; Developmental Biology/Aging; Food; Gene expression; Gene Expression Profiling; Genes, Helminth; Genetics; Genetics and Genomics/Gene Expression; Heat-Shock Response - genetics; Heat-Shock Response - physiology; Inactivation, Metabolic; Lipid Metabolism; Medical research; Metabolism; Metals, Heavy - metabolism; Metals, Heavy - toxicity; Models, Biological; Molecular Biology/Transcription Initiation and Activation; Mutation; Nematodes; Nutrition; Protein Subunits; Proteins; RNA Interference; Trans-Activators - antagonists & inhibitors; Trans-Activators - chemistry; Trans-Activators - genetics; Trans-Activators - metabolism; Xenobiotics - metabolism; Xenobiotics - toxicity
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1000021

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.