Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 31, Pages 13736-13741Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1001399107
Keywords
coactivator-associated arginine methyltransferase 1; HuR; neural differentiation; embryonic stem cells
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Funding
- Formacion de Profesorado Universitario Spanish Research Programme Fellowship
- Red TerCel
- Consejeria de Salud Junta de Andalucia
- Spanish Ministry of Health [PI061267, PS09/02454]
- Spanish National Research Council (Consejo Superior de Investigaciones Cientificas) [200820I172]
- European Union [LSHG-CT-2006-018739]
- Obra Social Cajastur, Spain
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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.
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