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La liasa ATP-citrato enlaza el metabolismo celular con la acetilación de la histona
Kathryn E Wellen1, Georgia Hatzivassiliou, Uma M Sachdeva
1Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Science (New York, N.Y.)
|May 23, 2009
Resumen
La acetilación de la histona de los mamíferos depende de la adenosina trifosfato (ATP) - citrato liasa (ACL), que vincula el metabolismo de los nutrientes con la expresión génica. ACL convierte el citrato derivado de la glucosa en acetil-CoA, crucial para la modificación de la histona.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- La epigenética es la epigenética.
Sus antecedentes:
- Los eucariotas unicelulares utilizan el acetato para la acetilación de la histona a través de las sintetasas de acetil-CoA.
- Los metazoos utilizan principalmente glucosa y tienen un acetato extracelular limitado, lo que requiere vías alternativas para la acetilación de histonas.
Objetivo del estudio:
- Para investigar la enzima primaria responsable de la acetilación de histonas en las células de mamíferos.
- Determinar el papel de la adenosina trifosfato (ATP) -citrato liasa (ACL) en la vinculación del metabolismo de los nutrientes a la acetilación de las histonas y la expresión génica.
Principales métodos:
- Se utilizaron modelos de cultivo de células de mamíferos.
- Evaluación de los niveles de acetilación de histonas bajo diferentes condiciones de glucosa y estimulación del factor de crecimiento.
- Investigó la actividad enzimática de la ATP-citrato liasa (ACL) y su papel en la producción de acetil-CoA.
Principales resultados:
- La acetilación de la histona en las células de mamíferos depende de la ATP-citrato liasa (ACL).
- La LCA es esencial para el aumento de la acetilación de histonas durante la estimulación y diferenciación del factor de crecimiento.
- La disponibilidad de glucosa influye en la acetilación de histonas a través de un mecanismo dependiente de la LCA.
Conclusiones:
- La actividad de la LCA es necesaria para vincular el metabolismo de nutrientes inducido por el factor de crecimiento con la acetilación de histonas.
- ACL actúa como una enzima crítica que conecta el metabolismo celular con la regulación epigenética y la expresión génica en los mamíferos.
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