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SHREC, un complejo de efectores para el silenciamiento transcripcional heterocromático
Tomoyasu Sugiyama1, Hugh P Cam, Rie Sugiyama
1Laboratory of Molecular Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cell
|February 10, 2007
Resumen
Un nuevo complejo proteico, SHREC, media el silenciamiento de genes de transcripción en la heterocromatina de la levadura de fisión. Este complejo regula el posicionamiento de los nucleosomas para establecer estructuras de cromatina de orden superior esenciales para el silenciamiento de genes.
Área de la Ciencia:
- La epigenética es la epigenética.
- Biología Molecular Biología Molecular
- Biología de la cromatina Biología de la cromatina
Sus antecedentes:
- La heterocromatina se asocia tradicionalmente con el silenciamiento genético transcripcional (TGS).
- Los hallazgos recientes en levadura de fisión sugieren un papel para el silenciamiento de genes posttranscripcionales (PTGS) mediado por ARNi en la heterocromatina, desafiando la primacía de TGS.
- Los mecanismos moleculares precisos que subyacen a las TGS heterocromáticas siguen siendo incompletamente entendidos.
Objetivo del estudio:
- Identificar y caracterizar la maquinaria molecular responsable del silenciamiento de genes transcripcionales heterocromáticos en la levadura de fisión.
- Para dilucidar la composición y la función del complejo efector mediando TGS en heterocromatina.
- Investigar los mecanismos de reclutamiento y las funciones reguladoras de este complejo en la organización de la cromatina.
Principales métodos:
- Purificación bioquímica y caracterización de los complejos proteicos de la levadura de fisión.
- Análisis genético para evaluar la función de las proteínas identificadas en el silenciamiento de genes.
- Estudios de inmunoprecipitación y localización de la cromatina para determinar la distribución compleja.
- Ensayos de posicionamiento de nucleosomas y análisis de estructuras de cromatina de orden superior.
Principales resultados:
- Identificación del SHREC (Silencing Hub and Regulatory Complex) como un complejo de efectores multienzima que media en el SGT heterocromático.
- SHREC comprende un cuarteto de núcleos (Clr1, Clr2, Clr3, Mit1) distribuidos en los dominios de la heterocromatina.
- SHREC utiliza las actividades de la histona desacetilasa (Clr3) y el remodelador de cromatina (Mit1) para establecer TGS y regula el posicionamiento del nucleosoma para el ensamblaje de cromatina de orden superior.
- SHREC se recluta a los telómeros a través de la maquinaria Ccq1 / Taz1 y RNAi, y a los sitios eucromáticos a través de mecanismos dependientes de Swi6 / HP1.
Conclusiones:
- SHREC es un complejo de efectores clave para el silenciamiento de genes de transcripción en la heterocromatina de levadura de fisión.
- Las actividades del complejo, incluida la regulación de la posición de los nucleosomas, son críticas para establecer la heterocromatina funcional.
- SHREC integra distintas vías de reclutamiento para garantizar su localización y función en diferentes regiones genómicas.
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