Sirtuin 1 regulation of developmental genes during differentiation of stem cells

被引：135

作者：

Calvanese, Vincenzo ^{[1
]}

Lara, Ester ^{[2
]}

Suarez-Alvarez, Beatriz ^{[3
]}

Abu Dawud, Raed ^{[4
,5
]}

Vazquez-Chantada, Mercedes ^{[6
]}

Luz Martinez-Chantar, Maria ^{[6
]}

Embade, Nieves ^{[6
]}

Lopez-Nieva, Pilar ^{[7
]}

Horrillo, Angelica ^{[8
]}

Hmadcha, Abdelkrim ^{[9
]}

Soria, Bernat ^{[8
]}

Piazzolla, Daniela ^{[9
]}

Herranz, Daniel ^{[9
]}

Serrano, Manuel ^{[9
]}

Maria Mato, Jose ^{[6
]}

Andrews, Peter W. ^{[4
,5
]}

Lopez-Larrea, Carlos ^{[3
]}

Esteller, Manel ^{[7
]}

Fraga, Mario F. ^{[1
]}

机构：

[1] CSIC, Dept Immunol & Oncol, Ctr Nacl Biotecnol, Madrid 28049, Spain

[2] Univ Oviedo, Hosp Univ Cent Asturias, Inst Univ Oncol Principado Asturias, Canc Epigenet Lab, E-33006 Oviedo, Spain

[3] Hosp Univ Cent Asturias, Unidad Histocompatibilidad, Oviedo 33006, Spain

[4] Univ Sheffield, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England

[5] Univ Sheffield, Ctr Stem Cell Biol, Sheffield S10 2TN, S Yorkshire, England

[6] Ctr Invest Biomed Red & Enfermedades Hepat & Dige, Ctr Invest Cooperat & Biociencias, Bizkaia 48170, Spain

[7] Bellvitge Biomed Res Inst, Canc Epigenet & Biol Program, Barcelona 08907, Spain

[8] Andalusian Ctr Mol Biol & Regenerat Med, Seville 41092, Spain

[9] Spanish Natl Canc Res Ctr, Tumor Suppress Grp, Madrid 28029, Spain

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 31期

关键词：

coactivator-associated arginine methyltransferase 1; HuR; neural differentiation; embryonic stem cells; SIR2-ALPHA PROTEIN; HUR; PHOSPHORYLATION; RESTRICTION; METHYLATION; EXPRESSION; STABILITY; H4;

D O I：

10.1073/pnas.1001399107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：13736 / 13741

页数：6

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