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Una red transcripcional extendida para la pluripotencia de las células madre embrionarias
Jonghwan Kim1, Jianlin Chu, Xiaohua Shen
1Department of Pediatric Oncology, Boston, MA 02115, USA.
Cell
|March 25, 2008
Resumen
Los investigadores mapearon los factores de transcripción clave que controlan la pluripotencia de las células madre embrionarias. Descubrieron que el número de factores que se unen a los promotores de genes dicta si los genes permanecen activos o reprimidos durante la diferenciación.
Área de la Ciencia:
- Biología de las células madre Biología de las células madre
- La epigenética es la epigenética.
- Las redes de factores de transcripción son redes de factores de transcripción.
Sus antecedentes:
- Las células madre embrionarias (ES) poseen pluripotencia, la capacidad de diferenciarse en cualquier tipo de célula.
- Se sabe que un número limitado de factores de transcripción mantienen este estado crucial.
- Se carece de una comprensión completa de la red reguladora que rige la pluripotencia.
Objetivo del estudio:
- Identificar globalmente promotores objetivo de nueve factores clave de transcripción en células ES de ratón.
- Para aclarar la red reguladora que mantiene la pluripotencia.
- Comprender el papel de los factores de transcripción en las decisiones del destino de las células ES.
Principales métodos:
- Identificación de todo el genoma de los sitios de unión del factor de transcripción.
- Análisis de la ocupación del factor de transcripción en promotores de genes en células ES de ratón.
- Correlación de la unión del factor de transcripción con la actividad génica y el estado de diferenciación.
Principales resultados:
- Promotores objetivo identificados para Oct4, Sox2, Klf4, c-Myc, Nanog, Dax1, Rex1, Zpf281 y Nac1.
- Se demostró que los promotores unidos por pocos factores están inactivos / reprimidos, mientras que los unidos por >4 factores están activos en células pluripotentes y se reprimen al diferenciarse.
- Propuso una jerarquía transcripcional para los factores de reprogramación, distinguiendo los objetivos c-Myc de otros.
Conclusiones:
- El número de factores de transcripción que se unen a un promotor es un determinante crítico de la actividad génica en las células pluripotentes.
- Una red transcripcional compleja, con roles distintos para factores como c-Myc, mantiene la pluripotencia.
- Este estudio proporciona un recurso valioso para investigar los mecanismos subyacentes a la pluripotencia y la diferenciación.
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