The Mediator subunit MDT-15 confers metabolic adaptation to ingested material.
PLoS Genet
; 4(2): e1000021, 2008 Feb 29.
Article
en En
| MEDLINE
| ID: mdl-18454197
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-15NHR-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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transactivadores
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Caenorhabditis elegans
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Proteínas de Caenorhabditis elegans
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2008
Tipo del documento:
Article