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El papel esencial de la glicosiltransferasa sxc/Ogt en la represión del policombo
Maria Cristina Gambetta1, Katarzyna Oktaba, Jürg Müller
1Gene Expression Programme, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Science (New York, N.Y.)
|May 30, 2009
Resumen
El gen de Drosophila super sex combs (sxc) codifica la transferasa N-acetilglucosamina (O-GlcNAc) ligada a la O (Ogt). La modificación de O-GlcNAc es crucial para que las proteínas del grupo Polycomb mantengan la represión transcripcional durante el desarrollo.
Área de la Ciencia:
- Biología del desarrollo Biología del desarrollo.
- La epigenética es la epigenética.
- Biología Molecular Biología Molecular
Sus antecedentes:
- Las proteínas del grupo de policombos (PcG) son esenciales represores transcripcionales conservados.
- Las proteínas PcG regulan la expresión génica crítica para el desarrollo animal y vegetal.
Objetivo del estudio:
- Para identificar la función molecular del gen de Drosophila super sex combs (sxc).
- Investigar el papel de Sxc/Ogt en la represión transcripcional mediada por el grupo Polycomb.
Principales métodos:
- Perfilado de todo el genoma en Drosophila para identificar proteínas modificadas por GlcNAc.
- Análisis de los mutantes sxc/Ogt-null para evaluar el impacto en la represión de Polycomb.
- Ensayos de glicosilación in vivo para las proteínas del grupo Polycomb.
Principales resultados:
- El gen sxc de Drosophila codifica la transferasa O-GlcNAc (Ogt).
- Las proteínas modificadas por GlcNAc se enriquecen en los elementos de respuesta de Polycomb.
- La proteína poliomeótica es glicosilada por Sxc/Ogt.
- Los mutantes sxc/Ogt-null exhiben pérdida de GlcNAcilación vinculada a O y no logran mantener la represión de PcG.
- Los complejos de proteínas PcG se unen a los sitios objetivo en los mutantes, pero se pierde la represión.
Conclusiones:
- La glicosilación mediada por Sxc/Ogt de Polyhomeotic es crítica para la represión de Polycomb en Drosophila.
- La O-GlcNAcilación es un mecanismo regulador clave para el control del desarrollo mediado por PcG.
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