GENE REGULATION. Discrete functions of nuclear receptor Rev-erbα couple metabolism to the clock.
Science
; 348(6242): 1488-92, 2015 Jun 26.
Article
en En
| MEDLINE
| ID: mdl-26044300
ABSTRACT
Circadian and metabolic physiology are intricately intertwined, as illustrated by Rev-erbα, a transcription factor (TF) that functions both as a core repressive component of the cell-autonomous clock and as a regulator of metabolic genes. Here, we show that Rev-erbα modulates the clock and metabolism by different genomic mechanisms. Clock control requires Rev-erbα to bind directly to the genome at its cognate sites, where it competes with activating ROR TFs. By contrast, Rev-erbα regulates metabolic genes primarily by recruiting the HDAC3 co-repressor to sites to which it is tethered by cell type-specific transcription factors. Thus, direct competition between Rev-erbα and ROR TFs provides a universal mechanism for self-sustained control of the molecular clock across all tissues, whereas Rev-erbα uses lineage-determining factors to convey a tissue-specific epigenomic rhythm that regulates metabolism tailored to the specific need of that tissue.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regulación de la Expresión Génica
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Ritmo Circadiano
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Proteínas CLOCK
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Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares
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Relojes Circadianos
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Histona Desacetilasas
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Metabolismo
Límite:
Animals
Idioma:
En
Revista:
Science
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos