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El proteosoma restringe la transcripción permisiva en los loci génicos específicos de los tejidos en las células
Henrietta Szutorisz1, Andrew Georgiou, László Tora
1Gene Regulation and Chromatin Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 ONN, UK. henrietta.szutorisz@csc.mrc.ac.uk
Cell
|December 28, 2006
Resumen
El proteosoma previene la activación genética incorrecta en las células madre embrionarias mediante la regulación de la unión al factor de transcripción. La inhibición de la actividad del proteasoma conduce a una expresión génica no intencionada, destacando su papel en el mantenimiento de la potencia de las células madre.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Biología del desarrollo Biología del desarrollo.
Sus antecedentes:
- La diferenciación de las células madre se basa en programas precisos de expresión génica.
- Los factores de transcripción y la ARN polimerasa II orquestan la activación génica en las regiones reguladoras.
Objetivo del estudio:
- Investigar el papel del proteosoma en la regulación de la transcripción génica en las células madre embrionarias (CE).
- Para determinar cómo la actividad del proteasoma impacta el factor de transcripción y la ARN polimerasa II que se une a los elementos reguladores.
Principales métodos:
- Inhibición química y mediada por siRNA de la actividad del proteasoma.
- Análisis de los perfiles de unión del factor de transcripción y la ARN polimerasa II.
- Evaluación de la unión de las subunidades del proteasoma en las células ES y después del knockdown de RNAi.
Principales resultados:
- La inhibición del proteasoma aumentó el factor de transcripción y la unión de la ARN polimerasa II.
- La inhibición condujo a la activación de promotores crípticos, lo que indica una transcripción aberrante.
- La evidencia sugiere un ensamblaje dirigido del proteosoma 26S en elementos reguladores específicos.
Conclusiones:
- El proteosoma regula dinámicamente el factor de transcripción y la rotación de Pol II en los dominios génicos de las células ES.
- La actividad del proteasoma restringe la transcripción permisiva, manteniendo los genes en un estado potenciado.
- Esta regulación es crucial para prevenir la activación prematura de genes durante el desarrollo temprano de las células madre.
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