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

Publication Type:

Journal Article

Source:

PLoS genetics, Volume 4, Issue 2, p.e1000021 (2008)

Keywords:

2008, Adaptation, Physiological, Animals, Basic Sciences Division, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Center-Authored Paper, Food, Gene Expression Profiling, Genes, Helminth, Genomics Core Facility, Heat-Shock Response, lipid metabolism, Metabolic Detoxication, Drug, Metals, Heavy, Models, Biological, Mutation, Protein Subunits, RNA Interference, Shared Resources, Trans-Activators, Xenobiotics

Abstract:

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.