The Mediator Subunit MDT-15 Confers Metabolic Adaptation to Ingested Material e1000021

• Published in: PLoS genetics Vol. 4; no. 2
• Main Authors: Taubert, Stefan, Hansen, Malene, Gilst, Marc RVan, Cooper, Samantha B, Yamamoto, Keith R
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 01.02.2008
• Subjects: Gene expression; Genetics; Medical research; Metabolism; Nematodes; Proteins
• ISSN: 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1000021

In eukaryotes, RNA polymerase II (PolII) dependent gene expression requires accessory factors termed transcriptional coregulators. One coregulator that universally contributes to PolII-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.