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La activación de la fase S del promotor de la histona H2B por OCA-S, un complejo de coactivador que contiene GAPDH
Lei Zheng1, Robert G Roeder, Yan Luo
1Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Cell
|July 31, 2003
Resumen
Los investigadores identificaron OCA-S, un complejo proteico crucial para la transcripción de la histona H2B dependiente de la fase S. Su componente p38, una forma nuclear de la gliceraldehído-3-fosfato deshidrogenasa, se une a Oct-1 y vincula la transcripción a la regulación del ciclo celular y el estado metabólico.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- La transcripción del gen de la histona está estrictamente regulada durante el ciclo celular, particularmente durante la fase S para la replicación del ADN.
- Oct-1 es un factor de transcripción involucrado en la regulación de varios procesos celulares, incluida la expresión génica de la histona.
Objetivo del estudio:
- Identificar y caracterizar los coactivadores involucrados en la transcripción de la histona H2B dependiente de la fase S.
- Para dilucidar los mecanismos moleculares que vinculan la expresión génica de la histona a la regulación del ciclo celular y el metabolismo celular.
Principales métodos:
- Coinmunoprecipitación para identificar las interacciones de las proteínas.
- Inmunoprecipitación de la cromatina para evaluar el reclutamiento de promotores.
- Pruebas de transcripción in vitro e in vivo.
- Análisis bioquímicos para estudiar la actividad enzimática y la dependencia del cofactor.
Principales resultados:
- Se aisló y caracterizó OCA-S, un coactivador multicomponente esencial para la transcripción de la histona H2B dependiente de la fase S.
- Identificó p38 como un componente clave de OCA-S, que se une a Oct-1 y es reclutado para el promotor H2B durante la fase S.
- Se demostró que p38 es una forma nuclear de la gliceraldehído-3-fosfato deshidrogenasa, con su función modulada por NAD (((+) y NADH.
- Se demostró que OCA-S interactúa con NPAT, vinculando la transcripción de histonas a los reguladores del ciclo celular.
Conclusiones:
- OCA-S es un regulador crítico de la transcripción de la histona H2B específica de la fase S.
- Los hallazgos vinculan la transcripción del gen histona con el control del ciclo celular y el estado redox celular a través del componente p38 de OCA-S.
- Este trabajo proporciona una base para la comprensión de la expresión génica coordinada de la histona y su acoplamiento a la replicación del ADN.
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