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WDR5 se asocia con la histona H3 metilada en K4 y es esencial para la metilación H3 K4 y el desarrollo de los
Joanna Wysocka1, Tomek Swigut, Thomas A Milne
1Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10021, USA.
Cell
|June 18, 2005
Resumen
La proteína WDR5 de repetición WD40 reconoce la metilación de la histona H3 lisina 4 (K4), una marca vinculada a la activación del gen. WDR5 es crucial para la trimetilación H3 K4, la activación del gen HOX y el desarrollo de los vertebrados.
Área de la Ciencia:
- La epigenética es la epigenética.
- Biología Molecular Biología Molecular
- Biología del desarrollo Biología del desarrollo.
Sus antecedentes:
- La metilación de la histona H3 lisina 4 (K4) es una marca epigenética clave asociada con la activación transcripcional en los eucariotas.
- La familia de proteínas MLL (MLL1, MLL2, hSet1) son metiltransferasas H3 K4 involucradas en la regulación de los genes.
Objetivo del estudio:
- Investigar el papel de la proteína WDR5 de repetición WD40 en la metilación H3 K4 y sus consecuencias funcionales.
- Para determinar si WDR5 reconoce directamente modificaciones específicas de histonas.
Principales métodos:
- Ensayos bioquímicos para evaluar la interacción entre WDR5 y colas de histona H3 metiladas y nucleosomas.
- Agotamiento de WDR5 en células humanas para evaluar su papel en la trimetilación H3 K4 y la expresión del gen HOX.
- Estudios funcionales en renacuajos de Xenopus laevis para evaluar el papel en el desarrollo de WDR5.5.
Principales resultados:
- WDR5 se une directamente a la histona H3 di- y trimetilada en K4, y a los nucleosomas H3-K4-dimetilados.
- WDR5 es esencial para el reclutamiento del complejo de la metiltransferasa al H3 K4-dimetilado y para la trimetilación global H3 K4.
- El agotamiento de WDR5 en las células humanas conduce a una activación alterada del gen HOX.
- WDR5 es crítico para el desarrollo de los vertebrados, con el agotamiento que causa defectos de desarrollo y altera la expresión del gen Hox en renacuajos de Xenopus.
Conclusiones:
- El WDR5 actúa como lector de la marca de metilación H3 K4, reconociendo específicamente el K4 di- y trimetilado.
- Este mecanismo de reconocimiento es vital para reclutar complejos de metiltransferasa H3 K4, lo que facilita la activación génica.
- WDR5 es indispensable para el desarrollo normal de los vertebrados, destacando la importancia conservada de este mecanismo epigenético de lectura-escritura.
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