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La recombinación genética está dirigida lejos de los elementos genómicos funcionales en ratones
Kevin Brick1, Fatima Smagulova, Pavel Khil
1National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892, USA.
Nature
|June 5, 2012
Resumen
La proteína PRDM9 suele dirigir la recombinación genética a puntos de acceso específicos. En su ausencia, la recombinación todavía ocurre, pero se redirige a los promotores de genes y otros sitios genómicos.
Área de la Ciencia:
- Genética La genética.
- Biología Molecular Biología Molecular
- Biología Reproductiva Biología Reproductiva.
Sus antecedentes:
- La recombinación genética durante la meiosis es crucial para la gametogénesis y la especiación.
- El dominio PR que contiene 9 (PRDM9) es una histona metiltransferasa vinculada a la recombinación y especiación de los mamíferos.
- Se cree que el dominio de dedo de zinc de PRDM9 especifica los puntos calientes de recombinación a través de la unión específica de la secuencia.
Objetivo del estudio:
- Mapear y analizar la distribución en todo el genoma de los sitios de iniciación de la recombinación en ratones knockout Prdm9 y diferentes cepas de ratones.
- Para aclarar el papel de PRDM9 en la determinación de la ubicación de los puntos calientes de recombinación.
- Para comprender los mecanismos de la recombinación independiente del PRDM9.
Principales métodos:
- Mapeo de todo el genoma de los sitios de inicio de la recombinación.
- Análisis de los patrones de recombinación en ratones con knockout Prdm9, ratones de tipo salvaje con diferentes alelos y híbridos de F.
- Investigación de las modificaciones histónicas, específicamente la trimetilación H3K4, en los sitios de recombinación.
Principales resultados:
- PRDM9 dicta la ubicación de casi todos los puntos calientes de recombinación de mamíferos, excepto en la región pseudo-autosómica (PAR).
- Los puntos calientes de recombinación persisten en ratones knockout Prdm9, localizados en las marcas de trimetilación H3K4.
- En ausencia de PRDM9, la recombinación se inicia predominantemente en los promotores y otros sitios de trimetilación H3K4 independientes de PRDM9.
Conclusiones:
- PRDM9 es el principal determinante de las posiciones de los puntos calientes de recombinación en el genoma del ratón.
- PRDM9 juega un papel inesperado en la prevención de la recombinación en promotores de genes y elementos genómicos funcionales.
- El estudio revela una función novedosa de PRDM9 en guiar la recombinación lejos de las regiones reguladoras esenciales.
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