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
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
收藏
页码:13736 / 13741
页数:6
相关论文
共 32 条
  • [1] Phosphorylation of HuR by Chk2 regulates SIRT1 expression
    Abdelmohsen, Kotb
    Pullmann, Rudolf, Jr.
    Lai, Ashish
    Kim, Hyeon Ho
    Galban, Stefanie
    Yang, Xiaoling
    Blethrow, Justin D.
    Walker, Mark
    Shubert, Jonathan
    Gillespie, David A.
    Furneaux, Henry
    Gorospe, Myriam
    [J]. MOLECULAR CELL, 2007, 25 (04) : 543 - 557
  • [2] Functional gene screening in embryonic stem cells implicates Wnt antagonism in neural differentiation
    Aubert, J
    Dunstan, H
    Chambers, I
    Smith, A
    [J]. NATURE BIOTECHNOLOGY, 2002, 20 (12) : 1240 - 1245
  • [3] Feeder-free culture of human embryonic stem cells in conditioned medium for efficient genetic modification
    Braam, Stefan R.
    Denning, Chris
    Matsa, Elena
    Young, Lorraine E.
    Passier, Robert
    Mummery, Christine L.
    [J]. NATURE PROTOCOLS, 2008, 3 (09) : 1435 - 1443
  • [4] Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice
    Cheng, HL
    Mostoslavsky, R
    Saito, S
    Manis, JP
    Gu, YS
    Patel, P
    Bronson, R
    Appella, E
    Alt, FW
    Chua, KF
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (19) : 10794 - 10799
  • [5] Principles of Glomerular Organization in the Human Olfactory Bulb - Implications for Odor Processing
    Maresh, Alison
    Gil, Diego Rodriguez
    Whitman, Mary C.
    Greer, Charles A.
    [J]. PLOS ONE, 2008, 3 (07):
  • [6] Identification of a target RNA motif for RNA-binding protein HuR
    de Silanes, IL
    Zhan, M
    Lal, A
    Yang, XL
    Gorospe, M
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (09) : 2987 - 2992
  • [7] Overexpression of HuR, a nuclear-cytoplasmic shuttling protein, increases the in vivo stability of ARE-containing mRNAs
    Fan, XHC
    Steitz, JA
    [J]. EMBO JOURNAL, 1998, 17 (12) : 3448 - 3460
  • [8] Role of HuR in skeletal myogenesis through coordinate regulation of muscle differentiation genes
    Figueroa, A
    Cuadrado, A
    Fan, J
    Atasoy, U
    Muscat, GE
    Muñoz-Canoves, P
    Gorospe, M
    Muñoz, A
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (14) : 4991 - 5004
  • [9] JNK2-dependent regulation of SIRT1 protein stability
    Ford, Jack
    Ahmed, Shafiq
    Allison, Simon
    Jiang, Ming
    Milner, Jo
    [J]. CELL CYCLE, 2008, 7 (19) : 3091 - 3097
  • [10] Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer
    Fraga, MF
    Ballestar, E
    Villar-Garea, A
    Boix-Chornet, M
    Espada, J
    Schotta, G
    Bonaldi, T
    Haydon, C
    Ropero, S
    Petrie, K
    Iyer, NG
    Pérez-Rosado, A
    Calvo, E
    Lopez, JA
    Cano, A
    Calasanz, MJ
    Colomer, D
    Piris, MA
    Ahn, N
    Imhof, A
    Caldas, C
    Jenuwein, T
    Esteller, M
    [J]. NATURE GENETICS, 2005, 37 (04) : 391 - 400