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El bromodomaín Gcn5 coordina la remodelación de los nucleosomas
P Syntichaki1, I Topalidou, G Thireos
1Institute of Molecular Biology and Biotechnology, FORTH, and Department of Biology, University of Crete, Heraklion, Greece.
Nature
|April 4, 2000
Resumen
El bromodomaín de las histonas acetiltransferasas (HAT) enlaza la acetilación de histonas con la remodelación del nucleosoma. Esta interacción es crucial para la activación transcripcional Swi2-dependiente, estabilizando el complejo Swi/Snf.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- La epigenética es la epigenética.
- Regulación genética Reglamento genético.
Sus antecedentes:
- El acceso del factor de transcripción a los promotores eucariotas requiere la modificación de la estructura de la cromatina por complejos multiproteicos.
- Las histonas acetiltransferasas (HAT) y las ATPasas (como Swi2 en Swi/Snf) son clases clave de complejos de remodelación.
- El vínculo funcional entre los HAT y los complejos Swi/Snf en la regulación de promotores sigue sin estar claro.
Objetivo del estudio:
- Para investigar el papel de la bromodomaína, un módulo HAT conservado, en la vinculación de la acetilación de histonas a la posterior remodelación del nucleosoma.
- Determinar si la unión de lisina acetilada con bromodomaína es esencial in vivo para la actividad de HAT y los eventos posteriores.
Principales métodos:
- Utilizó un sistema promotor específico para estudiar in vivo los requisitos funcionales del bromodomaín Gcn5.
- Evaluó la necesidad de residuos de bromodomaína críticos para la unión in vitro de acetil-lisina para la acetilación de histonas mediada por Gcn5.
- Se evaluó el impacto de las mutaciones de bromodomaínas en la remodelación y activación transcripcional de los nucleosomas Swi2-dependientes.
Principales resultados:
- Los residuos de bromodomaína esenciales para la unión de acetil-lisina in vitro son prescindibles para la acetilación de histonas mediada por Gcn5 in vivo.
- Estos residuos específicos de bromodomaínos son críticos para la posterior remodelación del nucleosoma dependiente de Swi2 y la activación transcripcional.
- Se demostró que el bromodomaín Gcn5 estabiliza el complejo Swi/Snf en el promotor.
Conclusiones:
- El bromodomain actúa como un eslabón crucial entre la acetilación de histonas y la maquinaria de remodelación de nucleosomas.
- La interacción bromodomaína-acetil-lisina es esencial para apuntar y estabilizar el complejo Swi/Snf, facilitando la activación transcripcional.
- Este estudio aclara un mecanismo clave en la regulación coordinada de la expresión génica eucariota.
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Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
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