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El PAD4 humano regula los niveles de metilación de la histona arginina a través de la desmetilación
Yanming Wang1, Joanna Wysocka, Joyce Sayegh
1Department of Genetic Medicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
Science (New York, N.Y.)
|September 4, 2004
Resumen
La peptidylarginina humana deiminasa 4 (PAD4) elimina los grupos metilo de los residuos de histona arginina, convirtiéndolos en citrulina. Esta modificación epigenética regula la expresión génica, particularmente para los genes receptivos al estrógeno.
Área de la Ciencia:
- La epigenética es la epigenética.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- La metilación de la histona regula la expresión génica, pero las enzimas desmetiladoras eran desconocidas.
- La metilación de la arginina en las histonas está vinculada a la regulación epigenética de los genes.
Objetivo del estudio:
- Para identificar las enzimas que desmetilan los residuos de histona arginina.
- Para investigar el papel de la peptidylarginina desiminasa 4 (PAD4) en la desmetilación de la histona arginina y la regulación génica.
Principales métodos:
- Ensayos enzimáticos con PAD4.4 en humanos.
- Análisis de las modificaciones histónicas en los granulocitos HL-60 y las células MCF-7.
- Investigando el efecto de la PAD4 en la metilación y la citrulinación de las histonas H3 y H4.
Principales resultados:
- La PAD4 humana fue identificada como una enzima que convierte la histona metilarginina en citrulina.
- PAD4 se dirige a múltiples sitios de arginina en las histonas H3 y H4, incluidos los metilados por CARM1 y PRMT1.
- La actividad de PAD4 disminuyó la metilación de la histona arginina y aumentó la citrulinación en las células HL-60.
- La actividad de PAD4 se correlacionó con la regulación transcripcional de los genes receptivos al estrógeno en las células MCF-7.
Conclusiones:
- PAD4 media la expresión génica mediante la regulación de la metilación de la histona arginina y la citrulinación.
- PAD4 representa un nuevo regulador epigenético dirigido a las modificaciones de la histona arginina.
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