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Regulación de la acetilación de histonas en el núcleo por el esfingosina-1-fosfato
Nitai C Hait1, Jeremy Allegood, Michael Maceyka
1Department of Biochemistry and Molecular Biology and the Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
Science (New York, N.Y.)
|September 5, 2009
Resumen
La esfingosina-1-fosfato (S1P) actúa dentro de las células, regulando la expresión génica mediante la inhibición de las histonas desacetilasas (HDAC). Este descubrimiento vincula S1P a los mecanismos epigenéticos que controlan los genes como p21 y c-fos.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- La epigenética es la epigenética.
- La bioquímica es la bioquímica.
Sus antecedentes:
- El Sphingosine-1-phosphate (S1P) es un mediador lipídico con funciones intracelulares conocidas.
- Los mecanismos de las acciones intracelulares de S1P, independientemente de los receptores de la superficie celular, siguen siendo en gran medida desconocidos.
- La esfingosina quinasa 2 (SphK2) genera el S1P. intracelular.
Objetivo del estudio:
- Para dilucidar los mecanismos intracelulares de la acción de S1P.
- Para investigar el papel de SphK2 en la regulación de la expresión génica.
- Para identificar objetivos intracelulares directos de S1P.
Principales métodos:
- Los ensayos de coinmunoprecipitación detectan las interacciones proteína-proteína.
- Pruebas enzimáticas para medir la actividad de la histona desacetilasa.
- Inmunoprecipitación de cromatina (ChIP) para evaluar el enriquecimiento de promotores de genes.
Principales resultados:
- La esfingosina quinasa 2 (SphK2) se asocia con la histona H3 y regula la acetilación de la histona.
- S1P se une directamente e inhibe las histonas desacetilasas HDAC1 y HDAC2.
- SphK2 y S1P se enriquecen en los promotores de los genes p21 y c-fos, mejorando la acetilación y transcripción de histonas.
Conclusiones:
- Las histonas desacetilasas (HDAC) son objetivos intracelulares directos de S1P.
- El S1P nuclear, a través de SphK2, juega un papel en la regulación epigenética de la expresión génica.
- Este estudio revela un nuevo vínculo entre la señalización S1P y el control epigenético de los genes diana.
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