info:eu-repo/semantics/article
Elovl3: a model gene to dissect homeostatic links between the circadian clock and nutrition status
Fecha
2006-12Registro en:
Anzulovich Miranda, Ana Cecilia; Mir, Alain; Brewer, Michelle; Ferreyra, Gabriela; Vinson, Charles; et al.; Elovl3: a model gene to dissect homeostatic links between the circadian clock and nutrition status; American Society for Biochemistry and Molecular Biology; Journal of Lipid Research Papers In Press; 47; 12; 12-2006; 2690-2700
0022-2275
1539-7262
CONICET Digital
CONICET
Autor
Anzulovich Miranda, Ana Cecilia
Mir, Alain
Brewer, Michelle
Ferreyra, Gabriela
Vinson, Charles
Baler, Ruben
Resumen
The ELOVL3 protein is a very long-chain fatty acid elongase found in liver, skin, and brown adipose tissues. Circadian expression of the Elovl3 gene in the liver is perturbed in mutant CLOCK mice but persists in mice with severe hepatic dysfunction. A reliance on an intact clock, combined with the refractoriness to liver decompensation and the finding of a robust sexually dimorphic pattern of expression, evince a particularly complex mode of transcriptional control. The Elovl3 gene upstream region was repressed by RevErbα and activated by sterol-regulatory element binding protein-1 (SREBP1) transcription factors. We propose that the temporal coordination of RevErbα and SREBP1 activities integrates clock and nutrition signals to drive a subset of oscillatory transcripts in the liver. Proteolytic activation of SREBP1 is circadian in the liver, and because the cycle of SREBP1 activation was reversed after restricting meals to the inactive phase of the day, this factor could serve as an acute sensor of nutritional state. SREBP1 regulates many known lipogenic and cholesterogenic circadian genes; hence, our results could explain how feeding can override brain-derived entraining signals in the liver. This mechanism would permit a rapid adjustment in the sequence of key aspects of the absorptive and postabsorptive phases in the liver.