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JARID2 y AEBP2 regulan PRC2 en presencia de H2AK119ub1 y otras modificaciones histónicas
Vignesh Kasinath1, Curtis Beck2, Paul Sauer3,4
1QB3 Institute, Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA. enogales@lbl.gov vigneshk@berkeley.edu.
Science (New York, N.Y.)
|January 22, 2021
Resumen
Los complejos represivos policombos (PRC1 y PRC2) regulan la identidad celular. Las nuevas estructuras cryo-EM revelan cómo JARID2 y AEBP2 reclutan PRC2 a H2AK119ub1, superando las marcas de histona inhibidoras.
Área de la Ciencia:
- La epigenética
- Biología molecular
- Biología estructural
Sus antecedentes:
- Los complejos represivos policombos 1 y 2 (PRC1 y PRC2) son reguladores epigenéticos cruciales de la identidad celular.
- El mecanismo de reclutamiento de PRC2 por H2AK119ub1 mediado por PRC1 no se entiende bien.
Objetivo del estudio:
- Para aclarar la base estructural del reclutamiento de PRC2 a H2AK119ub1 por los cofactores JARID2 y AEBP2.
- Comprender cómo estos cofactores modulan la actividad de PRC2 en respuesta a otras modificaciones histónicas.
Principales métodos:
- Determinación de la estructura del PRC2 mediante criomicroscopía electrónica (crio-EM) con JARID2, AEBP2 y un nucleosoma modificado.
- Ensayos bioquímicos para evaluar la estimulación mediada por cofactores de la actividad de la PRC2.
Principales resultados:
- Una estructura cryo-EM de alta resolución reveló cómo JARID2 y AEBP2 se unen al nucleosoma H2AK119ub1 e interactúan con PRC2.
- JARID2 estimula directamente la actividad de PRC2 a través de las interacciones con EED y H2AK119-ubiquitina.
- AEBP2 actúa como un andamio y su presencia, junto con JARID2, alivia parcialmente la inhibición por H3K4me3 y H3K36me3.
Conclusiones:
- JARID2 y AEBP2 son mediadores clave en el diálogo cruzado entre las modificaciones histónicas y la función PRC2.
- Estos cofactores juegan un papel crítico en la orientación de PRC2 y la modulación de su actividad para la regulación genética epigenética adecuada y la determinación de la identidad celular.
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