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El conjunto de co-transcripción2 metilación de la histona H3 lisina 36 recluta un complejo Rpd3 represivo
Michael-Christopher Keogh1, Siavash K Kurdistani, Stephanie A Morris
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cell
|November 16, 2005
Resumen
La histona desacetilasa Rpd3 de la levadura funciona en dos complejos. El complejo Rpd3C(S), con subunidades Rco1 y Eaf3, es reclutado por metilación de histonas mediada por Set2 para desacetilizar el ADN transcrito, regulando la expresión génica.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- La epigenética es la epigenética.
- Genética de la levadura Genética de la levadura
Sus antecedentes:
- La histona desacetilasa de levadura Rpd3 (dominio RPelA que contiene proteína 3) juega un papel crucial en la represión de la iniciación de la transcripción en los promotores.
- Rpd3 funciona dentro de distintos complejos de proteínas, lo que afecta sus funciones reguladoras.
Objetivo del estudio:
- Aclarar la composición y función de los dos distintos complejos que contienen Rpd3 en la levadura.
- Investigar el mecanismo por el cual Rpd3C(S) es reclutado en regiones transcritas y su papel en la regulación génica.
Principales métodos:
- Análisis bioquímicos para identificar los componentes complejos de Rpd3.
- Estudios genéticos para evaluar los fenotipos mutantes.
- Perfiles de expresión génica para medir cambios en la transcripción.
- Inmunoprecipitación de la cromatina (ChIP) para determinar las interacciones proteína-ADN.
- Análisis de la metilación de la histona.
Principales resultados:
- Rpd3 existe en dos complejos: Rpd3C(S) (pequeño) y Rpd3C(L) (grande).
- Rpd3C(S) contiene subunidades únicas Rco1 y Eaf3, y sus mutantes muestran fenotipos similares a los mutantes Set2.
- El cromosoma Eaf3 media el reclutamiento de Rpd3C(S a los nucleosomas H3K36-metilados, facilitando la desacetilación de las regiones transcritas.
- La eliminación de los genes Set2 o Rpd3C(S) evita la necesidad del factor de alargamiento positivo Bur1/Bur2.
Conclusiones:
- El complejo Rpd3C(S) se recluta para los genes transcritos activamente a través de la metilación de la histona H3 lisina 36 mediada por Set2.
- Este reclutamiento conduce a la desacetilación de las regiones transcritas, actuando como un mecanismo regulador negativo para la transcripción.
- La vía Set2-Rpd3C(S) es crítica para el control adecuado de la elongación de la transcripción en la levadura.
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