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Los factores de interacción SAGA limitan la subdifusión de los genes transcritos a la envoltura nuclear
Ghislain G Cabal1, Auguste Genovesio, Susana Rodriguez-Navarro
1Unité de Biologie Cellulaire du Noyau, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France.
Nature
|June 9, 2006
Resumen
La activación génica en la levadura hace que los genes GAL activos se muevan a lo largo de la envoltura nuclear. Este confinamiento dinámico está mediado por proteínas específicas, que vinculan la transcripción a la organización nuclear.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- La actividad génica se correlaciona con cambios en el posicionamiento nuclear.
- Los genes pueden ser reprimidos cuando están atados a la envoltura nuclear.
- Se han observado genes activados cerca de la periferia nuclear, pero los mecanismos no están claros.
Objetivo del estudio:
- Para investigar los mecanismos moleculares de reposicionamiento de genes durante la activación transcripcional.
- Para entender cómo el movimiento de los genes está restringido en la periferia nuclear.
- Explorar la relación entre la transcripción génica y la organización nuclear.
Principales métodos:
- Rastreo dinámico en 3D de los loci de un solo gen en células vivas de Saccharomyces cerevisiae.
- Hibridación de ARN-fluorescencia in situ (FISH) para evaluar la actividad transcripcional.
- Eliminación genética de proteínas clave (ADA2, NUP1) para estudiar su papel en el confinamiento de genes.
Principales resultados:
- La activación del gen GAL conduce a un movimiento restringido, un movimiento de deslizamiento 2D a lo largo de la envoltura nuclear.
- Los genes GAL confinados perifericamente muestran una mayor actividad transcripcional que los loci intranucleares.
- El confinamiento está mediado por los miembros del complejo SAGA (Sus1, Ada2) y el factor de exportación de ARNm Sac3, que enlazan los genes con el componente del complejo de poros nucleares Nup1.
- La eliminación de ADA2 o NUP1 interrumpe el confinamiento perinuclear sin afectar la transcripción.
Conclusiones:
- La activación transcripcional es necesaria pero no suficiente para el confinamiento del gen GAL en la periferia nuclear.
- Los genes GAL activos se amarran dinámicamente al lado interno del complejo de poros nucleares.
- Este fenómeno apoya la hipótesis del "gene gating", que vincula la actividad génica con la función de los poros nucleares.
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