Sirtuin 1 regulation of developmental genes during differentiation of stem cells

Vincenzo Calvanese, Ester Lara, Beatriz Suárez-Álvarez, Raed Abu Dawud, Mercedes Vázquez-Chantada, Maria Luz Martínez-Chantar, Nieves Embade, Pilar López-Nieva, Angelica Horrillo, Abdelkrim Hmadcha, Bernat Soria, Daniela Piazzolla, Daniel Herranz, Manuel Serrano, Jose María Mato, Peter W. Andrews, Carlos López-Larrea, Manel Esteller, Mario F. Fraga

Research output: Contribution to journalArticlepeer-review

123 Scopus citations

Abstract

The longevity-promoting NAD+-dependent class III histone deacetylase Sirtuin 1 (SIRT1) is involved in stem cell function by controlling cell fate decisionand/or byregulatingthe 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 developmentalgenes such as the neuroretinalmorphogenesis 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.

Original languageEnglish (US)
Pages (from-to)13736-13741
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number31
DOIs
StatePublished - Aug 3 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Coactivator-associated arginine methyltransferase 1
  • Embryonic stem cells
  • HuR
  • Neural differentiation

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