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Las proteínas que contienen el dominio SRA y SET vinculan la ocupación de la ARN polimerasa V con la metilación del
Lianna M Johnson1, Jiamu Du2, Christopher J Hale1
1Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Nature
|January 28, 2014
Resumen
Las proteínas SUVH2 y SUVH9 reclutan la ARN polimerasa V a los sitios de metilación del ADN, lo que permite el silenciamiento de genes epigenéticos específicos en las plantas. Este mecanismo se basa en sus dominios SRA que se unen al ADN metilado, no en la actividad catalítica.
Área de la Ciencia:
- La epigenética es la epigenética.
- Biología Molecular Vegetal Biología Molecular Vegetal
- El silenciamiento genético.
Sus antecedentes:
- La metilación del ADN dirigida por ARN es crucial para el silenciamiento de genes en las plantas.
- Este proceso involucra a pequeños ARN interferentes (siARN), ARN polimerasa IV (Pol IV) y Pol V. Este proceso también es conocido como ARN polimerasa.
- Los roles de SUVH2 y SUVH9 en las etapas aguas abajo no estaban claros.
Objetivo del estudio:
- Para dilucidar el mecanismo por el cual SUVH2 y SUVH9 funcionan en la metilación de ADN dirigida por ARN.
- Para determinar si SUVH2 y SUVH9 poseen actividad de metiltransferasa.
- Para entender cómo Pol V es reclutado para atacar sitios de metilación del ADN.
Principales métodos:
- Estudios de asociación de cromatina en todo el genoma.
- Determinación de la estructura cristalina de SUVH9.9.
- Ensayos de mutagenesis dirigida al sitio y ensayos de silenciamiento de genes.
- Experimentos de atado utilizando dominios de dedo de zinc.
Principales resultados:
- La asociación de Pol V en todo el genoma requiere redundantemente tanto SUVH2 como SUVH9.
- SUVH9 carece de la actividad catalítica típica de las metiltransferasas.
- SUVH2 y SUVH9 se unen al ADN metilado a través de los dominios SRA, reclutando Pol V.
- La pérdida de la metilación del ADN conduce a la redistribución de Pol V y la hipermetilación en nuevos sitios.
- Atar SUVH9 al ADN no metilado recluta Pol V e induce el silenciamiento.
Conclusiones:
- SUVH2 y SUVH9 actúan como adaptadores, reclutando Pol V a los sitios de metilación del ADN a través de la unión metilo-ADN.
- Estas proteínas carecen de actividad intrínseca de la metiltransferasa, funcionando en su lugar en el reclutamiento.
- Los hallazgos revelan un mecanismo para el silenciamiento de genes epigenéticos dirigidos en las plantas.
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