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Las funciones combinatorias del corepresor del receptor nuclear en la transcripción y el desarrollo
K Jepsen1, O Hermanson, T M Onami
1Howard Hughes Medical Institute, Department of Biology, University of California, San Diego, La Jolla 92093, USA.
Cell
|October 13, 2000
Resumen
El receptor nuclear corepresor 1 (N-CoR) es vital para el desarrollo de los metazoos, ya que regula tanto la represión como la activación de genes. Los estudios de deleción genética revelan N-CoRR.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología del desarrollo Biología del desarrollo.
- La epigenética es la epigenética.
Sus antecedentes:
- La represión transcripcional es esencial para el desarrollo de los metazoos.
- Los compresores del núcleo como N-CoR y SMRT son reguladores críticos.
- El N-CoR juega un papel clave en varios procesos de desarrollo.
Objetivo del estudio:
- Investigar el papel de N-CoR en la regulación transcripcional durante el desarrollo.
- Comprender la participación de N-CoR en las vías de represión y activación.
- Para dilucidar la función de los corepresores y las histonas desacetilasas en la regulación genética específica.
Principales métodos:
- Estudios de deleción de genes en ratones (ratones con el gen N-CoR eliminado).
- Análisis de patrones de transcripción en varios tejidos y tipos de células.
- Investigando el papel de N-CoR en la represión mediada por receptores nucleares y REST/NRSF.
- Examinando la función de N-CoR en la activación del elemento de respuesta del ácido retinoico.
Principales resultados:
- La deleción de N-CoR causó bloqueos del desarrollo en el SNC, los linajes de eritrocitos y timocitos.
- N-CoR es esencial para la represión activa a corto plazo por los receptores nucleares y MAD.
- Se requiere N-CoR para un subconjunto de eventos de represión a largo plazo mediados por REST/NRSF.
- Inesperadamente, se requieren N-CoR y una desacetilasa para la activación transcripcional de un elemento de respuesta del ácido retinoico.
Conclusiones:
- N-CoR es un mediador crítico de la regulación transcripcional genespecífica en el desarrollo.
- Combinaciones específicas de corepresores y histonas desacetilasas orquestan la actividad génica.
- Estos hallazgos ponen de relieve las funciones complejas y dependientes del contexto de los corepresores en los procesos de desarrollo.
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