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

doi:10.1073/pnas.1001399107

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 journal › Article › peer-review

124 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 language	English (US)
Pages (from-to)	13736-13741
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	107
Issue number	31
DOIs	https://doi.org/10.1073/pnas.1001399107
State	Published - Aug 3 2010
Externally published	Yes

All Science Journal Classification (ASJC) codes

General

Keywords

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

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Calvanese, V., Lara, E., Suárez-Álvarez, B., Dawud, R. A., Vázquez-Chantada, M., Martínez-Chantar, M. L., Embade, N., López-Nieva, P., Horrillo, A., Hmadcha, A., Soria, B., Piazzolla, D., Herranz, D., Serrano, M., Mato, J. M., Andrews, P. W., López-Larrea, C., Esteller, M., & Fraga, M. F. (2010). Sirtuin 1 regulation of developmental genes during differentiation of stem cells. Proceedings of the National Academy of Sciences of the United States of America, 107(31), 13736-13741. https://doi.org/10.1073/pnas.1001399107

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title = "Sirtuin 1 regulation of developmental genes during differentiation of stem cells",

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.",

keywords = "Coactivator-associated arginine methyltransferase 1, Embryonic stem cells, HuR, Neural differentiation",

author = "Vincenzo Calvanese and Ester Lara and Beatriz Su{\'a}rez-{\'A}lvarez and Dawud, {Raed Abu} and Mercedes V{\'a}zquez-Chantada and Mart{\'i}nez-Chantar, {Maria Luz} and Nieves Embade and Pilar L{\'o}pez-Nieva and Angelica Horrillo and Abdelkrim Hmadcha and Bernat Soria and Daniela Piazzolla and Daniel Herranz and Manuel Serrano and Mato, {Jose Mar{\'i}a} and Andrews, {Peter W.} and Carlos L{\'o}pez-Larrea and Manel Esteller and Fraga, {Mario F.}",

year = "2010",

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doi = "10.1073/pnas.1001399107",

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Calvanese, V, Lara, E, Suárez-Álvarez, B, Dawud, RA, Vázquez-Chantada, M, Martínez-Chantar, ML, Embade, N, López-Nieva, P, Horrillo, A, Hmadcha, A, Soria, B, Piazzolla, D, Herranz, D, Serrano, M, Mato, JM, Andrews, PW, López-Larrea, C, Esteller, M & Fraga, MF 2010, 'Sirtuin 1 regulation of developmental genes during differentiation of stem cells', Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 31, pp. 13736-13741. https://doi.org/10.1073/pnas.1001399107

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T1 - Sirtuin 1 regulation of developmental genes during differentiation of stem cells

AU - Calvanese, Vincenzo

AU - Lara, Ester

AU - Suárez-Álvarez, Beatriz

AU - Dawud, Raed Abu

AU - Vázquez-Chantada, Mercedes

AU - Martínez-Chantar, Maria Luz

AU - Embade, Nieves

AU - López-Nieva, Pilar

AU - Horrillo, Angelica

AU - Hmadcha, Abdelkrim

AU - Soria, Bernat

AU - Piazzolla, Daniela

AU - Herranz, Daniel

AU - Serrano, Manuel

AU - Mato, Jose María

AU - Andrews, Peter W.

AU - López-Larrea, Carlos

AU - Esteller, Manel

AU - Fraga, Mario F.

PY - 2010/8/3

Y1 - 2010/8/3

N2 - 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.

AB - 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.

KW - Coactivator-associated arginine methyltransferase 1

KW - Embryonic stem cells

KW - HuR

KW - Neural differentiation

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U2 - 10.1073/pnas.1001399107

DO - 10.1073/pnas.1001399107

M3 - Article

C2 - 20631301

SN - 0027-8424

VL - 107

SP - 13736

EP - 13741

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 31

ER -

Sirtuin 1 regulation of developmental genes during differentiation of stem cells

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