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La isomerización de la prolina de la histona H3 regula la metilación de la lisina y la expresión génica
Christopher J Nelson1, Helena Santos-Rosa, Tony Kouzarides
1Gurdon Institute and Department of Pathology, Tennis Court Road, Cambridge, CB2 1QR, UK.
Cell
|September 9, 2006
Resumen
La isomerización de la prolina por Fpr4 regula la metilación de las histonas. Esta nueva modificación no covalente de la histona controla la transcripción génica al antagonizar la metilación Set2 de H3K36.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- La epigenética es la epigenética.
Sus antecedentes:
- La isomerización cis-trans de la prolina es un mecanismo regulador clave en las vías de señalización celular.
- Las modificaciones de las histonas juegan un papel crucial en la regulación de la expresión génica y la estructura de la cromatina.
Objetivo del estudio:
- Para identificar y caracterizar las isomerasas de prolina involucradas en la modificación de la histona.
- Investigar el papel de la isomerización de la prolina en la regulación de la metilación de las histonas y la transcripción génica.
Principales métodos:
- Ensayos enzimáticos in vitro para estudiar la isomerización de la prolina y la metilación de la histona.
- Análisis bioquímico de la unión histona-cola por Fpr4.
- Experimentos in vivo en Saccharomyces cerevisiae para evaluar los efectos de la actividad de Fpr4 en la metilación de histonas y la expresión génica.
Principales resultados:
- Fpr4, una isomerasa de prolina, se une a las colas de histona H3 y H4 y cataliza la isomerización de los residuos de prolina H3 P30 y P38.
- La isomerización de H3 P38 es esencial para la metilación de K36, y la isomerización mediada por Fpr4 inhibe la metilación de H3 K36 dependiente de Set2 in vitro.
- La pérdida de la actividad catalítica de Fpr4 in vivo conduce a un aumento de la metilación de H3K36 y a una cinética transcripcional alterada.
Conclusiones:
- La isomerización de la prolina actúa como una nueva modificación no covalente de la histona que influye en la transcripción.
- La isomerización de prolina mediada por Fpr4 antagoniza la metilación de H3K36 por Set2, lo que demuestra el cruce entre estos mecanismos reguladores.
- El estado conformacional de H3 P38, regulado por Fpr4, es crítico para la metilación H3K36 mediada por Set2 y la subsiguiente regulación génica.
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