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Reclutamiento de complejos HAT por interacciones directas de activador con la subunidad Tra1 relacionada con ATM
1Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biology, Department of Chemistry, The Pennsylvania State University, 306 Althouse Laboratory, University Park, PA 16802, USA.
Science (New York, N.Y.)
|June 26, 2001
Resumen
Los activadores de transcripción ácida se unen directamente a Tra1p, una subunidad común a los complejos de histona acetiltransferasa SAGA y NuA4. La interrupción de esta interacción perjudica la transcripción específica del gen y la acetilación de la histona.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Regulación genética Reglamento genético.
- La epigenética es la epigenética.
Sus antecedentes:
- Los complejos de histona acetiltransferasa (HAT) como SAGA y NuA4 son cruciales para la transcripción génica.
- El reclutamiento de la actividad HAT a promotores de genes específicos es un paso regulador clave.
- La interacción entre los activadores de transcripción y los HAT es esencial para este reclutamiento.
Objetivo del estudio:
- Investigar la interacción directa entre los activadores de transcripción y los complejos SAGA y NuA4 HAT.
- Para identificar la subunidad específica de SAGA y NuA4 involucrada en la unión del activador.
- Para dilucidar las consecuencias funcionales de interrumpir la interacción activador-HAT.
Principales métodos:
- La cromatografía de afinidad se utilizó para identificar las proteínas que interactúan.
- Se realizaron experimentos de transferencia de etiquetas de foto-enlace cruzado para confirmar las interacciones directas.
- La mutagénesis dirigida al sitio se empleó para estudiar el papel de los dominios de proteínas específicas.
Principales resultados:
- Los activadores de la transcripción ácida interactúan directamente con Tra1p, una subunidad compartida de SAGA y NuA4.4.
- Las mutaciones en el extremo COOH de Tra1p abolieron la unión del activador.
- Estas mutaciones condujeron a defectos transcripcionales específicos del gen y a una reducción de la acetilación de la histona específica del promotor.
Conclusiones:
- La proteína Tra1 es un objetivo común y esencial para los activadores de transcripción que interactúan con los complejos SAGA y NuA4 HAT.
- La interacción directa con Tra1p es crítica para el reclutamiento de la actividad HAT y la posterior activación génica.
- Este estudio proporciona una visión mecanicista de la regulación de la transcripción por los complejos HAT.
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