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Transcripción divergente de los promotores activos
Amy C Seila1, J Mauro Calabrese, Stuart S Levine
1Koch Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Science (New York, N.Y.)
|December 6, 2008
Resumen
La mayoría de los genes inician la transcripción unidireccionalmente. Este estudio revela una transcripción divergente generalizada en promotores de genes codificadores de proteínas, con ARN cortos flanqueando regiones activas de promotores, lo que sugiere un estado de equilibrio para la regulación.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Genética La genética.
- La epigenética es la epigenética.
Sus antecedentes:
- La iniciación de la transcripción por la ARN polimerasa II (RNAPII) se ha considerado tradicionalmente unidireccional.
- Los mecanismos precisos que rigen la actividad del promotor y la regulación génica aún están bajo investigación.
Objetivo del estudio:
- Para investigar el fenómeno de la transcripción divergente en promotores de genes codificadores de proteínas.
- Para caracterizar la naturaleza y la ubicación genómica de los ARN asociados al sitio de inicio de la transcripción (ARN-TSSa).
Principales métodos:
- Análisis de la mancha del norte para detectar y caracterizar los ARN-TSSa.
- Inmunoprecipitación de cromatina (ChIP) para evaluar las modificaciones histónicas (H3K4me3, H3K79me2) y la ocupación de RNAPII en las regiones promotoras.
Principales resultados:
- Evidencia de una transcripción divergente generalizada, que produce ARN cortos de sentido y antisenso, flanqueando a los promotores activos.
- Los TSSa-ARN, que van desde 20-90 nucleótidos, exhiben sesgos posicionales distintos: picos antisenso aguas arriba y picos de sentido aguas abajo de los sitios de inicio de transcripción (TSS).
- Las marcas distintivas de iniciación de la transcripción (RNAPII, H3K4me3) se colocalizan con las posiciones de TSSa-RNA, mientras que las marcas de alargamiento (H3K79me2) se encuentran aguas abajo de las TSS.
Conclusiones:
- La transcripción divergente de corta distancia es una característica común de los promotores de genes que codifican proteínas activas.
- Esta transcripción divergente puede contribuir a mantener las regiones promotoras en un estado de equilibrio para la posterior regulación génica.
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