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La disminución de la histona antagoniza la metilación de la arginina
Graeme L Cuthbert1, Sylvain Daujat, Andrew W Snowden
1Gurdon Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, United Kingdom.
Cell
|September 2, 2004
Resumen
La disminución de la histona arginina por la peptidil arginina deiminasa 4 (PADI4) antagoniza la transcripción activa al prevenir la metilación de la arginina. Este nuevo proceso de desminación reprime la inducción génica, ofreciendo nuevos conocimientos sobre la regulación epigenética.
Área de la Ciencia:
- La epigenética es la epigenética.
- Biología Molecular Biología Molecular
- Regulación genética Reglamento genético.
Sus antecedentes:
- La metilación de la histona arginina está asociada con la transcripción activa de genes.
- La metiltransferasa CARM1 es reclutada por promotores como el pS2 para la activación transcripcional.
- Se introduce un proceso que se opone a la metilación, llamado deiminación.
Objetivo del estudio:
- Investigar el papel de la desaminación en la regulación génica.
- Para identificar la enzima responsable de la disminución de la histona arginina.
- Para determinar si la desaminación antagoniza la metilación de la arginina y afecta la transcripción.
Principales métodos:
- Caracterización de la actividad de la peptidil arginina desiminasa 4 (PADI4) en la histona H3.3.
- Evaluación del efecto de la disminución de PADI4 en la metilación de la arginina mediada por CARM1.
- In vivo promotor de experimentos dirigidos a evaluar el papel represivo de PADI4.
Principales resultados:
- PADI4 disminuye específicamente los residuos de arginina R2, R8, R17 y R26 en la cola de la histona H3.
- La disminución por PADI4 evita la metilación de la arginina por el CARM1.
- PADI4 reprime la inducción de genes mediada por receptores hormonales y es reclutado para promotores regulados hacia abajo.
Conclusiones:
- La disminución es un nuevo mecanismo epigenético que antagoniza la activación transcripcional mediada por la metilación de la arginina histona.
- La deiminación mediada por PADI4 juega un papel represivo en la regulación génica.
- La comprensión de la disminución proporciona nuevos objetivos para la intervención terapéutica en enfermedades que implican la expresión génica aberrante.
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