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Selectividad de los cofactores remodeladores de la cromatina para la transcripción activada por ligandos
1Department of Molecular and Cell Biology, Howard Hughes Medical Institute, 401 Barker Hall, University of California, Berkeley, CA 94720-3204, USA.
Nature
|January 10, 2002
Resumen
Los investigadores identificaron el cofactor PBAF, crucial para la actividad de los receptores de hormonas nucleares en la transcripción génica. Los complejos relacionados como SWI / SNF humano no mostraron esta potenciación, destacando la selectividad funcional en la regulación génica.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Regulación genética Reglamento genético.
- La bioquímica es la bioquímica.
Sus antecedentes:
- La transcripción génica de los eucariotas está dirigida por proteínas reguladoras y cofactores.
- La evaluación de las funciones de cofactor indirectamente en animales y células presenta desafíos.
Objetivo del estudio:
- Para purificar e identificar un cofactor de múltiples subunidades esencial para la transcripción génica mediada por el receptor de hormonas nucleares.
- Para investigar la selectividad funcional de complejos relacionados de remodelación de la cromatina.
Principales métodos:
- Utilizó una reacción de transcripción reconstituida integrada dependiente de la cromatina.
- Purificado e identificado un cofactor de subunidad múltiple (PBAF).
- Se evaluaron los efectos de PBAF, SWI/SNF humano y ACF en la transcripción.
Principales resultados:
- PBAF identificado como un cofactor necesario para la transactivación ligando-dependiente por los receptores de hormonas nucleares.
- Se ha demostrado que el SWI/SNF y el ACF humanos no potencian esta activación transcripcional específica.
- Se demostró que la activación del receptor de la hormona nuclear requiere factores asociados a la proteína de unión a TATA (TBP) (TAF) y cofactores ARC / CRSP.
Conclusiones:
- El PBAF es un cofactor clave para la transcripción mediada por el receptor de hormonas nucleares.
- Existe una selectividad funcional entre los complejos relacionados de remodelación de la cromatina.
- Se definió un conjunto más completo de factores para la activación transcripcional.
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