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Mecanismo de activación transcripcional por Sp1: evidencia para los coactivadores
1Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Cell
|June 29, 1990
Resumen
El factor de transcripción Sp1 requiere coactivadores para su activación, que están presentes en el TFIID parcialmente purificado pero ausentes en el TFIID purificado. Estos coactivadores actúan como adaptadores entre Sp1 y la maquinaria de transcripción.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Reglamento genético Reglamento genético.
- La bioquímica es la bioquímica.
Sus antecedentes:
- La iniciación de la transcripción es un proceso complejo que involucra numerosos factores proteicos.
- TFIID (Factor de Transcripción II D) es un factor de transcripción general crucial que se une a la caja TATA e inicia la transcripción.
- Los coactivadores son proteínas que mejoran la transcripción pero no se unen directamente al ADN.
Objetivo del estudio:
- Investigar el papel de los coactivadores en la activación de la transcripción mediada por Sp1.
- Para determinar si los coactivadores son componentes esenciales de TFIID o entidades separadas.
- Para explorar la especificidad de las especies de las interacciones coactivador-TFIID.
Principales métodos:
- Ensayos de transcripción reconstituidos utilizando fracciones TFIID parcialmente purificadas y purificadas.
- Experimentos con Sp1 (un factor de transcripción específico) y CTF (un coactivador).
- Utilizando proteínas TFIID clonadas de diferentes especies (Drosophila y levadura).
Principales resultados:
- Sp1 activa la transcripción de promotores que contienen TATA con TFIID semipurificado pero no con TFIID purificado.
- Las fracciones parcialmente purificadas de TFIID contienen coactivadores esenciales para la activación mediada por Sp1.
- Los coactivadores interactúan con la porción amino-terminal del TFIID, y estas interacciones son específicas de la especie.
- Se necesita una actividad distinta, separada de los coactivadores, para la activación de Sp1 en promotores sin TATA.
Conclusiones:
- Los coactivadores son necesarios como adaptadores moleculares entre los trans-activadores como Sp1 y la maquinaria de transcripción general.
- Estos coactivadores son distintos del propio TFIID y son prescindibles para la transcripción basal.
- Las interacciones coactivador-TFIID exhiben especificidad de especie, destacando la complejidad de la regulación de la transcripción en diferentes organismos.
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