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La variación en la unión al ADN del homeodomain revelada por el análisis de alta resolución de las preferencias de
Michael F Berger1, Gwenael Badis, Andrew R Gehrke
1Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Cell
|July 1, 2008
Resumen
Los investigadores mapearon las preferencias de unión al ADN de la mayoría de los hogares de ratones, descubriendo 65 actividades distintas. Este trabajo permite la predicción de los sitios de unión del homeodomain entre especies, ayudando a los estudios evolutivos.
Área de la Ciencia:
- La genómica es la genómica.
- Biología Molecular Biología Molecular
- Biología evolutiva Biología evolutiva.
Sus antecedentes:
- Los homeodomos son proteínas cruciales de unión al ADN involucradas en el desarrollo.
- A pesar de su importancia, sus patrones precisos de reconocimiento de secuencias de ADN no se comprenden completamente.
- Conservados en todas las especies, los homeodomains sugieren una fuerte selección evolutiva en sus especificidades de unión.
Objetivo del estudio:
- Determinar exhaustivamente las preferencias de unión al ADN de los homeodomains de ratón.
- Identificar la diversidad de las actividades de unión del ADN dentro de la familia del homeodomain.
- Desarrollar un modelo predictivo para los sitios de unión del homeodomain en diferentes especies.
Principales métodos:
- Se utilizó la secuenciación de alto rendimiento para determinar la unión de 168 homeodominios de ratón a todas las posibles secuencias de ADN de 8 bases.
- Se desarrolló un sistema computacional para predecir los sitios de unión del homeodomain.
- Se dedujeron perfiles de vinculación para los homeodominios de varias especies animales.
Principales resultados:
- Se generaron perfiles detallados de unión al ADN para la mayoría de los homeodomains de ratón.
- Se identificaron al menos 65 actividades distintas de unión al ADN entre los homeodominios de ratones.
- El sistema computacional predijo con precisión los sitios de unión en organismos evolutivamente distantes como Drosophila y C. elegans.
- Se dedujeron perfiles completos de unión de 8 meros para la mayoría de los homeodomaines animales conocidos.
Conclusiones:
- La especificidad de unión al ADN del homeodominio es rica y compleja, con variaciones significativas.
- Es probable que la variación en el reconocimiento de secuencias contribuya a la diversidad funcional y al éxito evolutivo de los homeodomains.
- Este estudio proporciona un recurso de alta resolución para comprender la función y la evolución del homeodomain.
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