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UpSET recluta complejos HDAC y restringe la accesibilidad de la cromatina y la acetilación en las regiones promotoras
Hector Rincon-Arano1, Jessica Halow, Jeffrey J Delrow
1Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Cell
|November 27, 2012
Resumen
El estudio identifica upSET, un regulador de la transcripción en Drosophila, que previene la propagación de las marcas de cromatina activa. Su ausencia conduce a un aumento del ruido transcripcional y la esterilidad femenina.
Área de la Ciencia:
- La epigenética y la regulación génica.
- Biología del desarrollo Biología del desarrollo.
- Biología de la cromatina Biología de la cromatina
Sus antecedentes:
- La expresión génica del desarrollo depende de las interacciones genéticas y epigenéticas.
- Las proteínas del dominio SET son reguladores transcripcionales conocidos.
- El complejo Rpd3/Sin3 está involucrado en la desacetilación de histonas.
Objetivo del estudio:
- Para caracterizar upSET, un nuevo regulador transcripcional que contiene dominio SET en Drosophila.
- Para investigar el papel de upSET en la accesibilidad de la cromatina y la expresión génica.
- Comprender la función de upSET en la oogénesis y la fertilidad femenina.
Principales métodos:
- Identificación y caracterización del gen y proteína upSET en Drosophila.
- Análisis de la accesibilidad de la cromatina y los patrones de acetilación de histonas en moscas mutantes de tipo salvaje y upSET.
- Evaluación de la expresión génica, incluido el ruido transcripcional y la activación de elementos repetitivos.
- Examen de los componentes de la vía de señalización de Notch durante la oogénesis en mutantes upSET.
Principales resultados:
- UpSET es un regulador transcripcional reclutado para los genes activos, que funciona dentro de un complejo Rpd3 / Sin3.
- UpSET restringe la accesibilidad de la cromatina y la acetilación de histonas a las regiones promotoras.
- La pérdida de upSET conduce a una mayor accesibilidad de la cromatina y marcas activas que se extienden a las regiones genéticas y flanqueantes.
- La ausencia de upSET da como resultado un aumento del ruido transcripcional, la activación de elementos repetitivos y la expresión génica fuera del objetivo.
- Las moscas mutantes upSET exhiben esterilidad femenina debido a la regulación al alza de los componentes de señalización de Notch durante la oogénesis.
Conclusiones:
- UpSET define una nueva clase de reguladores transcripcionales metazoares.
- UpSET es esencial para la transcripción de ajuste fino al limitar la propagación de la cromatina activa.
- La desregulación de la función upSET afecta la organización de la cromatina, la fidelidad de la expresión génica y el desarrollo reproductivo.
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