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hCAS/CSE1L se asocia con la cromatina y regula la expresión de algunos genes diana de p53
Tomoaki Tanaka1, Shuichi Ohkubo, Ichiro Tatsuno
1Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Cell
|August 28, 2007
Resumen
La proteína de susceptibilidad a la apoptosis celular humana (hCAS/CSE1L) se une a promotores de genes específicos, lo que influye en la transcripción mediada por p53 y en los resultados celulares como la apoptosis. Su regulación a la baja afecta la expresión génica y la metilación de las histonas.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- La epigenética es la epigenética.
Sus antecedentes:
- La proteína supresora de tumores p53 controla los genes cruciales para el destino celular, incluida la detención del crecimiento y la apoptosis.
- La transactivación selectiva del promotor por p53 es vital para estos resultados, pero sigue siendo poco comprendida.
- Comprender los factores que modulan la actividad del gen diana p53 es clave para descifrar las respuestas celulares.
Objetivo del estudio:
- Investigar el papel de la proteína de susceptibilidad a la apoptosis celular humana (hCAS/CSE1L) en la regulación genética mediada por p53.
- Para determinar si hCAS/CSE1L se asocia con los promotores objetivo de p53 e influye en su transcripción.
- Para aclarar las consecuencias funcionales de la unión hCAS/CSE1L en los resultados celulares y las modificaciones epigenéticas.
Principales métodos:
- Investigó la asociación de hCAS/CSE1L con promotores de genes diana de p53, incluido PIG3.
- Se evaluó el impacto de la regulación a la baja de hCAS/CSE1L en la transcripción génica y las tasas de apoptosis.
- Cambios analizados en los patrones de metilación de histonas, específicamente la metilación H3K27, después del silenciamiento hCAS/CSE1L.
Principales resultados:
- Se encontró que hCAS/CSE1L se asocia con un subconjunto de promotores objetivo de p53, como PIG3, independientemente de p53.
- Los niveles reducidos de hCAS/CSE1L condujeron a una disminución de la transcripción de sus promotores objetivo preferidos y a una disminución de la apoptosis.
- El silenciamiento de hCAS/CSE1L resultó en un aumento de la metilación de la histona H3 lisina 27 en el locus del gen PIG3.
Conclusiones:
- El CAS/CSE1L humano funciona como una proteína asociada a la cromatina que se une a genes específicos.
- hCAS/CSE1L juega un papel importante en la transcripción mediada por p53 y la determinación de los resultados celulares.
- El factor de transporte nucleocitoplasmático hCAS/CSE1L influye en la expresión génica a través de la unión al promotor y las modificaciones epigenéticas.
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