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Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
Published on: November 11, 2016
La acetilación mediada por el reloj de BMAL1 controla la función circadiana.
Jun Hirayama1, Saurabh Sahar, Benedetto Grimaldi
1Department of Pharmacology, School of Medicine, University of California Irvine, Irvine 92697-4625, California, USA.
Nature
|December 14, 2007
Resumen
La proteína CLOCK acetila su socio BMAL1, un paso clave en la regulación del reloj interno del cuerpo. Esta acetilación es crucial para el correcto funcionamiento de los ritmos circadianos y la expresión génica.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Cronobiología cronobiología.
- La epigenética es la epigenética.
Sus antecedentes:
- Los ritmos circadianos están regulados por circuitos de retroalimentación transcripción-traducción.
- El complejo CLOCK-BMAL1 activa la expresión génica, mientras que las criptocromos (Crys) la reprimen.
- CLOCK tiene una actividad intrínseca de la histona acetiltransferasa que influye en la expresión génica.
Objetivo del estudio:
- Para investigar la actividad de acetilación no histónica de CLOCK.
- Determinar el papel de la acetilación de BMAL1 en la regulación del ritmo circadiano.
Principales métodos:
- Análisis de la acetilación de BMAL1 en el hígado de ratón.
- Mutación del residuo de lisina 537 conservado en el BMAL1.
- Modelos celulares para evaluar la ritmicidad circadiana rescate.
Principales resultados:
- CLOCK acetila directamente el BMAL1 en la lisina 537.
- La acetilación de BMAL1 es rítmica y ocurre en el hígado del ratón.
- El BMAL1 acetilado mejora el reclutamiento de CRY1, promoviendo la represión transcripcional.
- Un BMAL1 mutado en K537R no logra restaurar el ritmo circadiano.
Conclusiones:
- La interacción enzimática CLOCK-BMAL1 es esencial para la maquinaria circadiana.
- La acetilación de BMAL1 por CLOCK es un mecanismo de regulación crítico.
- Esta modificación post-traducional ajusta la expresión génica circadiana.
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