RRC ID 4305
Author Taubert S, Hansen M, Van Gilst MR, Cooper SB, Yamamoto KR.
Title The Mediator subunit MDT-15 confers metabolic adaptation to ingested material.
Journal PLoS Genet.
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.
Volume 4(2)
Pages e1000021
Published 2008-2-29
DOI 10.1371/journal.pgen.1000021
PMID 18454197
PMC PMC2265483
MeSH 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* Food Gene Expression Profiling Genes, Helminth Heat-Shock Response / genetics Heat-Shock Response / physiology Inactivation, Metabolic Lipid Metabolism Metals, Heavy / metabolism Metals, Heavy / toxicity Models, Biological Mutation Protein Subunits RNA Interference Trans-Activators / antagonists & inhibitors Trans-Activators / chemistry Trans-Activators / genetics Trans-Activators / metabolism* Xenobiotics / metabolism Xenobiotics / toxicity
IF 5.224
Times Cited 45
C.elegans tm2182