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Proteínas que interactúan con los nucleosomas reguladas por la metilación del ADN y las histonas
Till Bartke1, Michiel Vermeulen, Blerta Xhemalce
1The Gurdon Institute, Department of Pathology, Cambridge, UK.
Cell
|October 30, 2010
Resumen
Los investigadores identificaron la intersección entre el ADN y la metilación de histonas, revelando cómo las proteínas como el complejo de reconocimiento de origen se unen a los nucleosomas. Este trabajo introduce un nuevo método para estudiar la dinámica de la modificación de la cromatina.
Área de la Ciencia:
- La epigenética y la biología de la cromatina.
- Biología Molecular Biología Molecular
- La Proteómica es la Proteómica.
Sus antecedentes:
- La función de la cromatina está regulada por modificaciones en el ADN y las histonas, que reclutan proteínas específicas.
- Comprender la interacción, o 'crosstalk', entre diferentes tipos de modificaciones es crucial para descifrar la regulación génica.
Objetivo del estudio:
- Para identificar proteínas que interactúan con los nucleosomas basadas en patrones de metilación de ADN e histonas.
- Para investigar el "crosstalk" entre la metilación del ADN y la metilación de la histona en el reclutamiento de proteínas.
- Establecer un nuevo método para analizar la dinámica de las interacciones de modificación de la cromatina.
Principales métodos:
- Utilizados nucleosomas metilados en el ADN y la histona H3 en un ensayo de afinidad.
- Análisis proteómico basado en SILAC (etiquetado de isótopos estables por aminoácidos en cultivos celulares) empleado.
- Desarrolló purificaciones de afinidad nucleosómica SILAC (SNAP) para la identificación de interactores de proteínas.
Principales resultados:
- Proteínas identificadas cuya unión al nucleosoma está modulada por la metilación de CpG, H3K4, H3K9 y H3K27.
- Descubrió el complejo de reconocimiento de origen (ORC), incluido LRWD1, como un interactor sensible a la metilación reclutado por la metilación combinada de ADN e histonas.
- Se descubrió que algunas proteínas de unión al metilo de la histona, como Fbxl11 / KDM2A, son interrumpidas por la metilación del ADN.
Conclusiones:
- Estableció SNAP como una herramienta valiosa para estudiar la interacción entre distintas modificaciones de la cromatina.
- Proporcionó información sobre cómo el ADN y la metilación de histonas regulan colectivamente la unión de proteínas a los nucleosomas.
- Caracterizados "perfiles" específicos de unión a proteínas influenciados por marcas epigenéticas combinadas.
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