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Chromatin Isolation by RNA Purification (ChIRP)
Published on: March 25, 2012
Un largo ARN no codificante mantiene la cromatina activa para coordinar la expresión génica homeótica
Kevin C Wang1, Yul W Yang, Bo Liu
1Howard Hughes Medical Institute, Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Nature
|March 23, 2011
Resumen
Los ARN no codificantes intergenicos largos (ARN linc) pueden activar la expresión génica. HOTTIP, un nuevo lincRNA, coordina la activación del gen HOXA mediante el reclutamiento de complejos modificadores de la cromatina, lo que demuestra un papel para los lincRNA en la regulación génica de largo alcance.
Área de la Ciencia:
- La genómica es la genómica.
- Biología Molecular Biología Molecular
- La epigenética es la epigenética.
Sus antecedentes:
- Los ARN no codificantes intergenicos largos (ARN linc) son cada vez más reconocidos por su papel en la regulación génica, principalmente en el silenciamiento de genes.
- La función de los lincRNAs en la activación génica, particularmente en los procesos de desarrollo, sigue siendo menos comprendida.
- La regulación coordinada de los genes vecinos, conocida como control de locus, es crucial para el desarrollo y la homeostasis.
Objetivo del estudio:
- Investigar el papel de los lincRNAs en la activación génica, centrándose específicamente en su posible participación en el control del locus.
- Identificar y caracterizar nuevos lincRNAs involucrados en la regulación de los grupos de genes Hox.
- Aclarar el mecanismo por el cual los lincRNA podrían mediar la activación génica de largo alcance.
Principales métodos:
- Identificación y caracterización de HOTTIP, un lincRNA transcrito desde el locus HOXA.
- Análisis de las interacciones de bucle cromosómico para evaluar la proximidad entre HOTTIP y sus genes diana.
- Pruebas bioquímicas para determinar la interacción del ARN HOTTIP con los complejos WDR5 y MLL.
- Evaluación de la trimetilación de la histona H3 y la lisina 4 y la transcripción génica en respuesta a la expresión HOTTIP.
Principales resultados:
- HOTTIP, un lincRNA de la punta 5' del locus HOXA, fue identificado.
- HOTTIP coordina la activación de los genes 5' HOXA in vivo.
- El bucle cromosómico facilita la interacción de HOTTIP con sus genes diana.
- El ARN HOTTIP se une directamente al WDR5, reclutando complejos WDR5/MLL para impulsar las modificaciones histónicas y la transcripción génica.
Conclusiones:
- lincRNAs pueden funcionar como intermediarios clave en la coordinación de la activación de genes de largo alcance.
- HOTTIP demuestra un nuevo mecanismo para la activación de genes mediada por lincRNA a través de la modificación de la cromatina.
- Este estudio pone de relieve el potencial de los lincRNAs en la organización de dominios de cromatina para la expresión génica coordinada durante el desarrollo.
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