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El coactivador compuesto ARC media la activación transcripcional dirigida por la cromatina

A M Näär¹, P A Beaurang, S Zhou

¹Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.

|May 11, 1999

Resumen

El cofactor reclutado por activador (ARC) mejora la activación génica al interactuar con los activadores transcripcionales. Este gran complejo de coactivadores, probablemente idéntico al DRIP, es crucial para la regulación de la expresión génica en los eucariotas.

Área de la Ciencia:

Biología Molecular Biología Molecular
Genética La genética.
La bioquímica es la bioquímica.

Sus antecedentes:

La activación de genes en eucariotas implica mecanismos complejos y proteínas que se unen al ADN.
El embalaje de la cromatina requiere actividades especializadas de orientación de la cromatina para la regulación génica.
Las células humanas utilizan cofactores de múltiples subunidades para la activación de genes selectivos de la cromatina.

Objetivo del estudio:

Para investigar la función y la composición del cofactor reclutado por activador (ARC).
Para determinar la interacción de ARC con varios activadores de la transcripción.
Para aclarar el papel de ARC en la potenciación de la activación de genes sinérgicos.

Principales métodos:

Ensayos de transcripción in vitro utilizando plantillas de ADN ensambladas con cromatina.
Análisis de las interacciones proteína-proteína entre ARC y activadores transcripcionales.
Caracterización de las subunidades complejas de ARC y comparación con cofactores conocidos.

Principales resultados:

ARC interactúa directamente con múltiples activadores, incluidos SREBP-1a, VP16 y p65.
ARC mejora significativamente la transcripción dirigida por estos activadores en las plantillas de cromatina.
El complejo ARC comprende más de 16 subunidades, con algunas nuevas y otras compartidas con CRSP, NAT y Mediator.
ARC es probablemente idéntico al cofactor receptor de hormonas nucleares DRIP.

Conclusiones:

ARC/DRIP es un coactivador compuesto de gran tamaño esencial para la estimulación transcripcional.
Esta familia de coactivadores es el objetivo de diversos activadores para mediar la expresión génica.
ARC/DRIP juega un papel importante en la compleja regulación de la activación del gen eucariota.

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