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Chromatin Immunoprecipitation from Human Embryonic Stem Cells
Published on: July 22, 2008
La cromatina distintiva en el esperma humano empaqueta genes para el desarrollo embrionario
Saher Sue Hammoud1, David A Nix, Haiying Zhang
1Howard Hughes Medical Institute, Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
Nature
|June 16, 2009
Resumen
El esperma retiene nucleosomas en ubicaciones clave del gen del desarrollo, desafiando las creencias anteriores sobre la contribución epigenética limitada. Estos nucleosomas retenidos llevan modificaciones específicas de histonas cruciales para la regulación del desarrollo embrionario temprano.
Área de la Ciencia:
- La epigenética es la epigenética.
- Biología del desarrollo Biología del desarrollo.
- Biología del esperma Biología del esperma
Sus antecedentes:
- Los espermatozoides humanos maduros usan principalmente protamina en lugar de nucleosomas, lo que lleva a la suposición de una influencia epigenética mínima de la cromatina espermática en el desarrollo del embrión.
- La comprensión previa sugería contribuciones epigenéticas limitadas de la cromatina del esperma debido al reemplazo de protamina de los nucleosomas.
Objetivo del estudio:
- Investigar la distribución y la importancia de los nucleosomas retenidos y sus modificaciones histónicas asociadas en el esperma humano.
- Para determinar si la cromatina del esperma retiene información epigenética relevante para el desarrollo embrionario.
Principales métodos:
- Análisis de la ocupación de los nucleosomas en el esperma humano.
- Mapeo de las modificaciones específicas de las histonas (H3K4me2, H3K4me3, H3K27me3) en los loci de desarrollo.
- Evaluación de los patrones de metilación del ADN en los promotores de esperma.
Principales resultados:
- Los nucleosomas retenidos se enriquecen significativamente en importantes loci de desarrollo, incluidos los grupos de genes impresos, los grupos de microARN y los grupos de genes HOX.
- Modificaciones específicas de histonas como H3K4me3 y H3K27me3 están localizadas en promotores del desarrollo y regiones reguladoras, que se correlacionan con los estados de expresión génica en embriones tempranos.
- Los promotores del desarrollo en el esperma generalmente están hipometilados, pero obtienen metilación durante la diferenciación.
Conclusiones:
- La cromatina del esperma retiene un extenso marcado epigenético, contrario a las suposiciones anteriores.
- Estas marcas epigenéticas están específicamente localizadas a los reguladores del desarrollo y están correlacionadas con los procesos clave del desarrollo, lo que sugiere un papel importante en el desarrollo embrionario.
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