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Un interruptor conformacional en HP1 libera autoinhibición para impulsar el conjunto de heterocromatina
Daniele Canzio1, Maofu Liao, Nariman Naber
1Department of Biochemistry and Biophysics, University of California San Francisco, California 94158, USA.
Nature
|March 15, 2013
Resumen
La proteína 1 de heterocromatina (HP1) que se une a los nucleosomas metilados cambia Swi6 de un estado autoinhibido a un estado de propagación-competente, crucial para el silenciamiento de genes y el ensamblaje de heterocromatina.
Área de la Ciencia:
- Biología de la cromatina Biología de la cromatina
- La epigenética es la epigenética.
- Mecanismos moleculares de la regulación génica.
Sus antecedentes:
- La heterocromatina metilada por histona H3 lisina 9 (H3K9) se extiende a regiones adyacentes, involucrando a la proteína 1 (HP1) de la heterocromatina.
- HP1 reconoce la cromatina metilada H3K9, oligomeriza y forma una plataforma para el silenciamiento de genes y la segregación cromosómica.
- El ensamblaje de HP1 en nucleosomas metilados y su versatilidad funcional no se comprenden bien.
Objetivo del estudio:
- Para dilucidar cómo las proteínas HP1 se ensamblan en plantillas nucleosómicas metiladas.
- Comprender el mecanismo detrás de la versatilidad funcional del complejo HP1-nucleosoma.
- Investigar el cambio de estado autoinhibido a propagación competente en Swi6 (HP1) que se une a los nucleosomas metilados.
Principales métodos:
- Reconstrucción basada en la criomicroscopia electrónica del complejo Swi6-nucleosoma.
- Estudios in vivo para evaluar el impacto de interrumpir el interruptor de estado autoinhibido / propagación competente.
Principales resultados:
- La unión de Swi6 a los nucleosomas metilados desencadena un cambio de un estado autoinhibido a un estado competente para la propagación.
- En el estado autoinhibido, una secuencia de imitación de histonas bloquea el reconocimiento de la marca de metilo del cromosoma.
- La autoinhibición se alivia al reconocer tanto la marca de metilo H3K9 como el ADN nucleosómico, exponiendo los "extremos pegajosos" para la propagación.
- La interrupción de este interruptor afecta el ensamblaje de la heterocromatina in vivo y el silenciamiento de genes.
Conclusiones:
- La interacción del nucleosoma HP1 implica un mecanismo de activación condicional, que cambia entre la autoinhibición y la difusión de la competencia.
- Este interruptor está regulado por el reconocimiento tanto de la marca de metilo H3K9 como del ADN nucleosómico.
- Los hallazgos revelan un nuevo mecanismo regulador para la propagación de la cromatina y el silenciamiento de genes.
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