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

PLoS genetics | Feb 29, 2008

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.

Pubmed ID: 18454197 RIS Download

Mesh terms: Adaptation, Physiological | Animals | Caenorhabditis elegans | Caenorhabditis elegans Proteins | Food | Gene Expression Profiling | Genes, Helminth | Heat-Shock Response | Inactivation, Metabolic | Lipid Metabolism | Metals, Heavy | Models, Biological | Mutation | Protein Subunits | RNA Interference | Trans-Activators | Xenobiotics

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Associated grants

  • Agency: NCI NIH HHS, Id: R01 CA020535
  • Agency: NCI NIH HHS, Id: 5R01CA020535-29

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