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La unión del producto hace cumplir la especificidad genómica de un policombo represivo complejo de levadura

Phillip A Dumesic¹, Christina M Homer¹, James J Moresco²

¹Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.

|December 24, 2014

Resumen

El sistema Polycomb en Cryptococcus neoformans establece los dominios represivos H3K27me. el sistema Polycomb en Cryptococcus neoformans establece los dominios represivos H3K27me. el sistema Polycomb en Cryptococcus neoformans establece los dominios represivos H3K27me. Interrumpiendo el Ccc1

Área de la Ciencia:

Biología de la cromatina Biología de la cromatina
La epigenética es la epigenética.
Microbiología molecular microbiología molecular.

Sus antecedentes:

El Complejo Represivo Polycomb 2 (PRC2) es crucial para establecer la metilación de H3K27 (H3K27me) y el silenciamiento de genes.
Comprender los mecanismos de la función de PRC2 y el reconocimiento de sustratos es clave para descifrar la regulación epigenética.
Cryptococcus neoformans ofrece un sistema modelo para estudiar las vías epigenéticas conservadas.

Objetivo del estudio:

Para caracterizar el complejo similar al PRC2 en Cryptococcus neoformans.
Para investigar el papel de la proteína Ccc1 del cromodomain en la deposición y el reconocimiento de H3K27me.
Para dilucidar cómo se establecen distintos dominios de cromatina por las enzimas modificadoras de histonas.

Principales métodos:

Purificación del complejo proteico similar al PRC2 de Cryptococcus neoformans. purificación del complejo proteico similar al PRC2 de Cryptococcus neoformans. purificación del complejo proteico similar al PRC2 de Cryptococcus neoformans.
Disrupción genética de las subunidades clave, incluidos los ortólogos EZH, EED y Ccc1.
Análisis de los patrones H3K27me y H3K9me utilizando inmunoprecipitación de cromatina y otras técnicas moleculares.
Investigando la interacción entre las marcas Ccc1 y H3K27me.

Principales resultados:

El complejo parecido al PRC2 de Cryptococcus neoformans contiene ortólogos de componentes PRC2 animales y una proteína de cromodomaín, Ccc1.1.
Ccc1 reconoce directamente el H3K27me.
La alteración de Ccc1 conduce a la redistribución de H3K27me, haciendo que coincida con los dominios de la heterocromatina H3K9me.
La pérdida de H3K9 metiltransferasa Clr4 también resulta en la pérdida de redistribuido H3K27me.

Conclusiones:

El reconocimiento de H3K27me por parte de la subunidad Ccc1 es esencial para limitar los dominios represivos a tipos específicos de cromatina.
El anclaje de complejos modificadores de la cromatina a sus productos puede evitar el diálogo cruzado con otros estados de la cromatina.
Este mecanismo explica cómo las enzimas con módulos de reconocimiento de productos pueden establecer dominios cromatínicos distintos a pesar de tener un sustrato común.

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