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Papel de la metilación de la histona H3 lisina 27 en el silenciamiento del grupo Polycomb
Ru Cao1, Liangjun Wang, Hengbin Wang
1Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.
Science (New York, N.Y.)
|September 28, 2002
Resumen
Este estudio identifica un vínculo directo entre la metilación de histonas y el silenciamiento de genes mediado por proteínas del grupo Polycomb (PcG). El complejo EED-EZH2 metila la histona H3 en la lisina 27, un paso clave para mantener el silencio genético.
Área de la Ciencia:
- La epigenética es la epigenética.
- Biología Molecular Biología Molecular
- Regulación genética Reglamento genético.
Sus antecedentes:
- Las proteínas del grupo policómbico (PcG) son cruciales para mantener el estado silencioso de los genes HOX.
- La metilación de la histona se ha implicado en el silenciamiento de genes a largo plazo.
- Anteriormente no se había establecido una conexión directa entre el silenciamiento mediado por PcG y la metilación de histonas.
Objetivo del estudio:
- Investigar los mecanismos moleculares que unen las proteínas del grupo Polycomb y la metilación de histonas.
- Para caracterizar la contraparte humana del complejo Drosophila ESC-E(Z) y su actividad enzimática.
- Para establecer un vínculo directo entre la metilación de histonas y el silenciamiento de genes mediado por PcG.
Principales métodos:
- Purificación y caracterización del complejo EED-EZH2 humano.
- Analiza para determinar la actividad de la histona metiltransferasa del complejo.
- Pruebas de inmunoprecipitación de cromatina (ChIP) para evaluar la metilación de H3-K27 y la unión de E(Z) in vivo.
- Análisis de la correlación entre la metilación H3-K27 y la represión génica.
Principales resultados:
- El complejo EED-EZH2 fue purificado y caracterizado como la contraparte humana ESC-E(Z).
- Se demostró que el complejo metila específicamente la histona nucleosómica H3 en la lisina 27 (H3-K27).
- Se encontró que la metilación de H3-K27 se colocaliza con y depende de la unión de E(Z) en el elemento de respuesta del policombo Ultrabithorax (Ubx) (PRE), que se correlaciona con la represión de Ubx.
- Se demostró que la metilación de H3-K27 facilita la unión de la proteína Polycomb (PC) (un componente de PRC1) a la cola amino-terminal de la histona H3.
Conclusiones:
- Estos hallazgos establecen un vínculo mecánico directo entre la metilación de histonas y el silenciamiento de genes mediado por el grupo Polycomb.
- La metilación de la histona H3 lisina 27 por el complejo EED-EZH2 es una marca epigenética crítica para la represión génica mediada por PcG.
- Este evento de metilación sirve como plataforma para el reclutamiento de otros componentes de PcG, como PRC1.1.
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