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Un mecanismo molecular para el reloj circadiano de retroalimentación negativa
Hao A Duong1, Maria S Robles, Darko Knutti
1Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Science (New York, N.Y.)
|June 18, 2011
Resumen
Los ritmos circadianos de los mamíferos dependen de las proteínas PERIOD (PER). Este estudio revela cómo los complejos PER, con PSF y SIN3A, reclutan histonas desacetilasas para reprimir la transcripción de Per1, aclarando un mecanismo clave de retroalimentación negativa.
Área de la Ciencia:
- Cronobiología cronobiología.
- Biología Molecular Biología Molecular
- La epigenética es la epigenética.
Sus antecedentes:
- Los ritmos circadianos de los mamíferos están regulados por un circuito de retroalimentación molecular que involucra a las proteínas CLOCK-BMAL1 y PERIOD (PER).
- El mecanismo molecular preciso de la retroalimentación negativa en los relojes circadianos de los eucariotas sigue siendo en gran medida desconocido.
Objetivo del estudio:
- Esclarecer el mecanismo molecular subyacente a la retroalimentación negativa en el reloj circadiano de los mamíferos.
- Identificar los constituyentes proteicos de los complejos PER y su papel en la represión transcripcional.
Principales métodos:
- Purificación y análisis de complejos de proteínas PER de tejidos de ratón.
- Identificación de las proteínas asociadas, incluido el PSF (factor de empalme asociado a la proteína de unión al tracto polipirimidino).
- Investigando el reclutamiento de SIN3A y las histonas desacetilasas al promotor Per1.
Principales resultados:
- La fibra de poliéster fue identificada como un componente del complejo PER.
- La PSF dentro del complejo PER recluta SIN3A, un andamio para los complejos inhibidores de la transcripción.
- El complejo PER entrega rítmicamente las histonas desacetilasas al promotor Per1, reprimiendo la transcripción de Per1.
Conclusiones:
- El complejo PER, a través de PSF y SIN3A, proporciona un mecanismo molecular para la retroalimentación negativa del reloj circadiano.
- Este estudio identifica una nueva función para el complejo PER en la regulación de la expresión génica circadiana a través de la modificación epigenética.
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