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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
Reclutamiento específico de la secuencia del co-represor de transcripción Cabin1 por el potenciador de miocitos
Aidong Han1, Fan Pan, James C Stroud
1Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, Colorado 80309-0215, USA.
Nature
|April 18, 2003
Resumen
Los factores de transcripción del factor potenciador de los miocitos-2 (MEF2) reclutan co-represores como Cabin1. Este estudio revela la estructura cristalina de MEF2B unido a Cabin1 y al ADN, aclarando un mecanismo clave para la represión de la transcripción.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología Estructural Biología estructural.
- Genética La genética.
Sus antecedentes:
- Los factores de transcripción del factor 2 potenciador de miocitos (MEF2) regulan las células T, las neuronas y las células musculares.
- MEF2 media la represión y la activación transcripcionales dependientes del calcio a través de coactivadores/co-represores.
- La represión transcripcional mediada por MEF2 está implicada en la hipertrofia de los cardiomiocitos.
Objetivo del estudio:
- Para dilucidar el mecanismo molecular del reclutamiento MEF2 de los co-represores de la transcripción.
- Para determinar la base estructural de la interacción entre MEF2B, Cabin1 y DNA.
Principales métodos:
- Cristalografía de rayos X del dominio MEF2B MADS-box/MEF2S unido a un motivo Cabin1 y al ADN.
- Análisis de la estructura del complejo ternario a una resolución de 2.2 A.
Principales resultados:
- Se determinó una estructura cristalina del dominio MEF2B MADS-box/MEF2S, el motivo Cabin1 y el ADN.
- Cabin1 forma una hélice alfa anfipática que une una ranura hidrofóbica en el dominio MEF2S.
- Se observó una interacción de triple hélice en el complejo ternario.
Conclusiones:
- La estructura cristalina revela una interacción estable del dominio MEF2S con la caja MADS.
- Se demuestra un mecanismo general para que el MEF2 recluya al ADN el co-represor Cabin1 y los HDAC de clase II.
- Este hallazgo proporciona información sobre la regulación transcripcional mediada por MEF2.
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