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El control de la metilación del ADN de CpNpG por la KRYPTONITE histona H3 metiltransferasa
James P Jackson1, Anders M Lindroth, Xiaofeng Cao
1Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles 90095, USA.
Nature
|March 19, 2002
Resumen
El silenciamiento de genes implica la formación de heterocromatina. El gen KRYPTONITE regula la metilación de histonas, que controla la metilación del ADN y el silenciamiento de genes en las plantas.
Área de la Ciencia:
- La epigenética y la regulación génica.
- Biología Molecular Vegetal Biología Molecular Vegetal
- Biología de la cromatina Biología de la cromatina
Sus antecedentes:
- El silenciamiento genético en los eucariotas está relacionado con la formación de heterocromatina, caracterizada por la metilación del ADN, la metilación de la histona H3 lisina 9 (H3 Lys 9) y la unión a la proteína 1 (HP1) de la heterocromatina.
- La relación precisa entre estas marcas epigenéticas, particularmente en las plantas, sigue siendo en gran medida no aclarada.
- En Neurospora crassa, la metilación del ADN actúa aguas abajo de la metilación H3 Lys 9, lo que sugiere una vía reguladora conservada.
Objetivo del estudio:
- Para identificar genes involucrados en la regulación del silenciamiento de genes y la formación de heterocromatina en Arabidopsis thaliana.
- Para dilucidar la relación entre la metilación de histonas y la metilación del ADN en el control del silenciamiento de genes.
- Para caracterizar la función del gen KRYPTONITE recientemente identificado en la regulación epigenética.
Principales métodos:
- Pantalla mutante para los supresores del silenciamiento genético en el locus. de Arabidopsis SUPERMAN (SUP).
- Aislamiento y caracterización del gen de la metiltransferasa KRYPTONITE.
- Análisis de los patrones de metilación del ADN (sitios de CpNpG) y la actividad de la retrotransposón en los mutantes de kryptonita con pérdida de función.
- Investigando las interacciones proteína-proteína entre los homólogos CMT3, HP1 y las histonas metiladas.
Principales resultados:
- Se identificó el gen KRYPTONITE, una nueva H3 Lys 9 metiltransferasa.
- Los alelos de kryptonita con pérdida de función exhiben una reducción de la metilación del ADN CpNpG y la reactivación de los retrotransposones endógenos, similar a los mutantes en la CHROMOMETHYLASE3 (CMT3).
- CMT3 interactúa con un homólogo de Arabidopsis HP1, que a su vez se une a las histonas metiladas.
Conclusiones:
- La metilación del ADN de CpNpG está epigenéticamente controlada por la metilación de la histona H3 Lys 9.
- La vía KRYPTONITE-CMT3-HP1 integra las señales de metilación de histonas y ADN para mantener el silenciamiento de genes y la estabilidad del genoma.
- Este estudio revela un mecanismo conservado que vincula la metilación de histonas con la metilación del ADN para el silenciamiento de genes en las plantas.
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