Sirtuin 1 regulation of developmental genes during differentiation of stem cells

The longevity-promoting NAD+-dependent class III histone deacetylase Sirtuin 1 (SIRT1) is involved in stem cell function by controlling cell fate decision and/or by regulating the p53-dependent expression of NANOG. We show that SIRT1 is down-regulated precisely during human embryonic stem cell diffe...

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Detalles Bibliográficos
Autores: Calvanese, Vincenzo, Lara, Ester, Suárez-Alvarez, Beatriz, Abu Dawud, Raed, Vázquez-Chantada, Mercedes, Martínez Chantar, Maria Luz, Embade, Nieves, López Nieva, Pilar, Horrillo, Angelica, Hmadcha, Abdelkrim, Soria Cubero, Berta, Piazzolla, Daniella, Herranz, Daniela, Serrano Marugán, Manuel, Mato, José M., Andrew, Peter W., López Larrea, Carlos, Esteller, Manel, Fraga, Mario F.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2010
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/179307
Acceso en línea:https://hdl.handle.net/2445/179307
Access Level:acceso abierto
Palabra clave:Diferenciació cel·lular
Cèl·lules mare embrionàries
Expressió gènica
Cell diferentiation
Embryonic stem cells
Gene expression
Descripción
Sumario:The longevity-promoting NAD+-dependent class III histone deacetylase Sirtuin 1 (SIRT1) is involved in stem cell function by controlling cell fate decision and/or by regulating the p53-dependent expression of NANOG. We show that SIRT1 is down-regulated precisely during human embryonic stem cell differentiation at both mRNA and protein levels and that the decrease in Sirt1 mRNA is mediated by a molecular pathway that involves the RNA-binding protein HuR and the arginine methyltransferase coactivator-associated arginine methyltransferase 1 (CARM1). SIRT1 down-regulation leads to reactivation of key developmental genes such as the neuroretinal morphogenesis effectors DLL4, TBX3, and PAX6, which are epigenetically repressed by this histone deacetylase in pluripotent human embryonic stem cells. Our results indicate that SIRT1 is regulated during stem cell differentiation in the context of a yet-unknown epigenetic pathway that controls specific developmental genes in embryonic stem cells.