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Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
Published on: December 19, 2018
Los ligandos diméricos definen un papel para los dominios de activación transcripcional en la reiniciación
S N Ho1, S R Biggar, D M Spencer
1Department of Pathology, Howard Hughes Medical Institute, Stanford University School of Medicine, California 94305, USA.
Nature
|August 29, 1996
Resumen
El mantenimiento de la transcripción génica en las células vivas requiere la presencia continua de un activador. Los ligandos sintéticos ofrecen un potente interruptor de encendido y apagado para controlar la transcripción génica en investigación y terapia.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Regulación genética Reglamento genético.
- Biología celular Biología celular.
Sus antecedentes:
- Los activadores transcripcionales eucariotas estabilizan el complejo de preiniciación, pero se debate su papel en el mantenimiento de la transcripción en curso (reiniciación).
- Los estudios in vitro arrojan resultados contradictorios sobre si los activadores son esenciales para la transcripción sostenida después de la formación del complejo de preiniciación.
Objetivo del estudio:
- Desarrollar un método para regular la transcripción génica en células vivas utilizando ligandos sintéticos.
- Investigar la necesidad de activadores de transcripción para mantener la transcripción de genes endógenos in vivo.
Principales métodos:
- Desarrollo de ligandos sintéticos homodiméricos y heterodimerizantes para controlar la asociación/disociación de los dominios de activación transcripcional con los promotores.
- Aplicación de este sistema para regular la transcripción genética endógena tanto en levaduras como en células humanas.
Principales resultados:
- Se demostró que se requiere la presencia continua del dominio de activación para mantener la transcripción génica endógena in vivo.
- Ligandos sintéticos establecidos como interruptores de encendido y apagado de transcripción efectivos en las células vivas.
Conclusiones:
- La presencia continua del dominio activador es esencial para la transcripción genética sostenida en las células eucariotas.
- Los sistemas de transcripción controlados por ligandos sintéticos proporcionan una herramienta versátil para aplicaciones experimentales y terapéuticas en el control de la expresión génica.
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