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La reubicación de genes dependiente de la metilación de ncRNA y Pc2 entre estructuras nucleares media programas de
Liuqing Yang1, Chunru Lin, Wen Liu
1Howard Hughes Medical Institute, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0648, USA.
Cell
|November 15, 2011
Resumen
La metilación de la proteína Polycomb 2 (Pc2) controla el movimiento de genes de crecimiento entre estructuras nucleares a través de ARN no codificantes (ARNnc). Esto vincula la arquitectura nuclear con la regulación de la expresión génica.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- La epigenética es la epigenética.
Sus antecedentes:
- Los núcleos eucariotas poseen estructuras vinculadas a los ARN no codificantes (ARNnc).
- El papel de estas estructuras en la regulación de la transcripción no se entiende bien.
Objetivo del estudio:
- Investigar la relación entre las estructuras arquitectónicas nucleares, los ncRNA y la regulación transcripcional.
- Para dilucidar el mecanismo por el cual los genes de control de crecimiento se reubican dentro del núcleo.
Principales métodos:
- Investigó el papel de la proteína Polycomb 2 (Pc2) en la metilación y la desmetilación.
- Estudió la unión de Pc2 a los ncRNAs TUG1 y MALAT1/NEAT2.2.
- Se examinó el impacto en la reubicación de genes entre los cuerpos de policombos (PCG) y los gránulos de intercromatina (ICG).
- Se analizaron los efectos en el conjunto de corepressor / coactivador y lectores de códigos de histona.
- Se evaluó el papel de la interacción NEAT2-Pc2 en la SUMOilación E2F1 y la activación de genes.
Principales resultados:
- El estado de metilación de Pc2 dicta la reubicación de los genes de control de crecimiento entre PcG e ICG.
- Pc2 se une a ncRNAs específicos (TUG1 en PcGs, MALAT1 / NEAT2 en ICGs) en función de su estado de metilación.
- Los ncRNA facilitan el ensamblaje de complejos proteicos reguladores e influyen en el reconocimiento de la marca de histona.
- La unión de NEAT2 al Pc2 no metilado promueve la SUMOilación E2F1, activando los genes de crecimiento.
Conclusiones:
- Una vía molecular conecta los ncRNA específicos de la estructura subnuclear y la metilación de proteínas a la reubicación de genes.
- Esta vía logra programas coordinados de expresión génica al vincular la arquitectura nuclear con el control de la transcripción.
- Los hallazgos revelan un nuevo mecanismo para regular los genes de control de crecimiento a través de cambios dinámicos en la organización nuclear.
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