The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine

Autores
Etchegaray, Jean Pierre; Chavez, Lukas; Huang, Yun; Ross, Kenneth N.; Choi, Jiho; Martinez Pastor, Barbara; Walsh, Ryan M.; Sommer, Cesar A.; Lienhard, Matthias; Gladden, Adrianne; Kugel, Sita; Silberman, Dafne Magalí; Ramaswamy, Sridhar; Mostoslavsky, Gustavo; Hochedlinger, Konrad; Goren, Alon; Rao, Anjana; Mostoslavsky, Raul
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
How embryonic stem cells (ESCs) commit to specific cell lineages and yield all cell types of a fully formed organism remains a major question. ESC differentiation is accompanied by large-scale histone and DNA modifications, but the relations between these epigenetic categories are not understood. Here we demonstrate the interplay between the histone deacetylase sirtuin 6 (SIRT6) and the ten-eleven translocation enzymes (TETs). SIRT6 targets acetylated histone H3 at Lys 9 and 56 (H3K9ac and H3K56ac), while TETs convert 5-methylcytosine into 5-hydroxymethylcytosine (5hmC). ESCs derived from Sirt6 knockout (S6KO) mice are skewed towards neuroectoderm development. This phenotype involves derepression of OCT4, SOX2 and NANOG, which causes an upregulation of TET-dependent production of 5hmC. Genome-wide analysis revealed neural genes marked with 5hmC in S6KO ESCs, thereby implicating TET enzymes in the neuroectoderm-skewed differentiation phenotype. We demonstrate that SIRT6 functions as a chromatin regulator safeguarding the balance between pluripotency and differentiation through Tet-mediated production of 5hmC.
Fil: Etchegaray, Jean Pierre. Harvard Medical School; Estados Unidos
Fil: Chavez, Lukas. La Jolla Institute for Allergy and Immunology; Estados Unidos. Texas A&M University; Estados Unidos
Fil: Huang, Yun. La Jolla Institute for Allergy and Immunology; Estados Unidos. Texas A&M University; Estados Unidos
Fil: Ross, Kenneth N.. Harvard Medical School; Estados Unidos
Fil: Choi, Jiho. Harvard Medical School; Estados Unidos
Fil: Martinez Pastor, Barbara. Harvard Medical School; Estados Unidos
Fil: Walsh, Ryan M.. Harvard Medical School; Estados Unidos
Fil: Sommer, Cesar A.. Boston University; Estados Unidos
Fil: Lienhard, Matthias. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Gladden, Adrianne. Massachusetts Institute of Technology; Estados Unidos
Fil: Kugel, Sita. Harvard Medical School; Estados Unidos
Fil: Silberman, Dafne Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Ramaswamy, Sridhar. Harvard Medical School; Estados Unidos. Boston University; Estados Unidos
Fil: Mostoslavsky, Gustavo. Boston University; Estados Unidos
Fil: Hochedlinger, Konrad. Harvard Medical School; Estados Unidos. Howard Hughes Medical Institute; Estados Unidos
Fil: Goren, Alon. Massachusetts Institute of Technology; Estados Unidos
Fil: Rao, Anjana. La Jolla Institute for Allergy and Immunology; Estados Unidos. University of California at San Diego; Estados Unidos
Fil: Mostoslavsky, Raul. Harvard Medical School; Estados Unidos
Materia
SITR6
STEM CELLS
DEVELOPMENT
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/45155
Acceder
id CONICETDig_92595e1d6116beddee04eed4d56dd7e5
oai_identifier_str oai:ri.conicet.gov.ar:11336/45155
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosineEtchegaray, Jean PierreChavez, LukasHuang, YunRoss, Kenneth N.Choi, JihoMartinez Pastor, BarbaraWalsh, Ryan M.Sommer, Cesar A.Lienhard, MatthiasGladden, AdrianneKugel, SitaSilberman, Dafne MagalíRamaswamy, SridharMostoslavsky, GustavoHochedlinger, KonradGoren, AlonRao, AnjanaMostoslavsky, RaulSITR6STEM CELLSDEVELOPMENThttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1How embryonic stem cells (ESCs) commit to specific cell lineages and yield all cell types of a fully formed organism remains a major question. ESC differentiation is accompanied by large-scale histone and DNA modifications, but the relations between these epigenetic categories are not understood. Here we demonstrate the interplay between the histone deacetylase sirtuin 6 (SIRT6) and the ten-eleven translocation enzymes (TETs). SIRT6 targets acetylated histone H3 at Lys 9 and 56 (H3K9ac and H3K56ac), while TETs convert 5-methylcytosine into 5-hydroxymethylcytosine (5hmC). ESCs derived from Sirt6 knockout (S6KO) mice are skewed towards neuroectoderm development. This phenotype involves derepression of OCT4, SOX2 and NANOG, which causes an upregulation of TET-dependent production of 5hmC. Genome-wide analysis revealed neural genes marked with 5hmC in S6KO ESCs, thereby implicating TET enzymes in the neuroectoderm-skewed differentiation phenotype. We demonstrate that SIRT6 functions as a chromatin regulator safeguarding the balance between pluripotency and differentiation through Tet-mediated production of 5hmC.Fil: Etchegaray, Jean Pierre. Harvard Medical School; Estados UnidosFil: Chavez, Lukas. La Jolla Institute for Allergy and Immunology; Estados Unidos. Texas A&M University; Estados UnidosFil: Huang, Yun. La Jolla Institute for Allergy and Immunology; Estados Unidos. Texas A&M University; Estados UnidosFil: Ross, Kenneth N.. Harvard Medical School; Estados UnidosFil: Choi, Jiho. Harvard Medical School; Estados UnidosFil: Martinez Pastor, Barbara. Harvard Medical School; Estados UnidosFil: Walsh, Ryan M.. Harvard Medical School; Estados UnidosFil: Sommer, Cesar A.. Boston University; Estados UnidosFil: Lienhard, Matthias. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Gladden, Adrianne. Massachusetts Institute of Technology; Estados UnidosFil: Kugel, Sita. Harvard Medical School; Estados UnidosFil: Silberman, Dafne Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Ramaswamy, Sridhar. Harvard Medical School; Estados Unidos. Boston University; Estados UnidosFil: Mostoslavsky, Gustavo. Boston University; Estados UnidosFil: Hochedlinger, Konrad. Harvard Medical School; Estados Unidos. Howard Hughes Medical Institute; Estados UnidosFil: Goren, Alon. Massachusetts Institute of Technology; Estados UnidosFil: Rao, Anjana. La Jolla Institute for Allergy and Immunology; Estados Unidos. University of California at San Diego; Estados UnidosFil: Mostoslavsky, Raul. Harvard Medical School; Estados UnidosNature Publishing Group2015-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfhttp://hdl.handle.net/11336/45155Etchegaray, Jean Pierre; Chavez, Lukas; Huang, Yun; Ross, Kenneth N.; Choi, Jiho; et al.; The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine; Nature Publishing Group; Nature Cell Biology; 17; 5; 5-2015; 545-5571465-7392CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/ncb3147info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/ncb3147info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593707/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:02:55Zoai:ri.conicet.gov.ar:11336/45155instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:02:56.267CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine
title The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine
spellingShingle The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine
Etchegaray, Jean Pierre
SITR6
STEM CELLS
DEVELOPMENT
title_short The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine
title_full The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine
title_fullStr The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine
title_full_unstemmed The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine
title_sort The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine
dc.creator.none.fl_str_mv Etchegaray, Jean Pierre
Chavez, Lukas
Huang, Yun
Ross, Kenneth N.
Choi, Jiho
Martinez Pastor, Barbara
Walsh, Ryan M.
Sommer, Cesar A.
Lienhard, Matthias
Gladden, Adrianne
Kugel, Sita
Silberman, Dafne Magalí
Ramaswamy, Sridhar
Mostoslavsky, Gustavo
Hochedlinger, Konrad
Goren, Alon
Rao, Anjana
Mostoslavsky, Raul
author Etchegaray, Jean Pierre
author_facet Etchegaray, Jean Pierre
Chavez, Lukas
Huang, Yun
Ross, Kenneth N.
Choi, Jiho
Martinez Pastor, Barbara
Walsh, Ryan M.
Sommer, Cesar A.
Lienhard, Matthias
Gladden, Adrianne
Kugel, Sita
Silberman, Dafne Magalí
Ramaswamy, Sridhar
Mostoslavsky, Gustavo
Hochedlinger, Konrad
Goren, Alon
Rao, Anjana
Mostoslavsky, Raul
author_role author
author2 Chavez, Lukas
Huang, Yun
Ross, Kenneth N.
Choi, Jiho
Martinez Pastor, Barbara
Walsh, Ryan M.
Sommer, Cesar A.
Lienhard, Matthias
Gladden, Adrianne
Kugel, Sita
Silberman, Dafne Magalí
Ramaswamy, Sridhar
Mostoslavsky, Gustavo
Hochedlinger, Konrad
Goren, Alon
Rao, Anjana
Mostoslavsky, Raul
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv SITR6
STEM CELLS
DEVELOPMENT
topic SITR6
STEM CELLS
DEVELOPMENT
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv How embryonic stem cells (ESCs) commit to specific cell lineages and yield all cell types of a fully formed organism remains a major question. ESC differentiation is accompanied by large-scale histone and DNA modifications, but the relations between these epigenetic categories are not understood. Here we demonstrate the interplay between the histone deacetylase sirtuin 6 (SIRT6) and the ten-eleven translocation enzymes (TETs). SIRT6 targets acetylated histone H3 at Lys 9 and 56 (H3K9ac and H3K56ac), while TETs convert 5-methylcytosine into 5-hydroxymethylcytosine (5hmC). ESCs derived from Sirt6 knockout (S6KO) mice are skewed towards neuroectoderm development. This phenotype involves derepression of OCT4, SOX2 and NANOG, which causes an upregulation of TET-dependent production of 5hmC. Genome-wide analysis revealed neural genes marked with 5hmC in S6KO ESCs, thereby implicating TET enzymes in the neuroectoderm-skewed differentiation phenotype. We demonstrate that SIRT6 functions as a chromatin regulator safeguarding the balance between pluripotency and differentiation through Tet-mediated production of 5hmC.
Fil: Etchegaray, Jean Pierre. Harvard Medical School; Estados Unidos
Fil: Chavez, Lukas. La Jolla Institute for Allergy and Immunology; Estados Unidos. Texas A&M University; Estados Unidos
Fil: Huang, Yun. La Jolla Institute for Allergy and Immunology; Estados Unidos. Texas A&M University; Estados Unidos
Fil: Ross, Kenneth N.. Harvard Medical School; Estados Unidos
Fil: Choi, Jiho. Harvard Medical School; Estados Unidos
Fil: Martinez Pastor, Barbara. Harvard Medical School; Estados Unidos
Fil: Walsh, Ryan M.. Harvard Medical School; Estados Unidos
Fil: Sommer, Cesar A.. Boston University; Estados Unidos
Fil: Lienhard, Matthias. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Gladden, Adrianne. Massachusetts Institute of Technology; Estados Unidos
Fil: Kugel, Sita. Harvard Medical School; Estados Unidos
Fil: Silberman, Dafne Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Ramaswamy, Sridhar. Harvard Medical School; Estados Unidos. Boston University; Estados Unidos
Fil: Mostoslavsky, Gustavo. Boston University; Estados Unidos
Fil: Hochedlinger, Konrad. Harvard Medical School; Estados Unidos. Howard Hughes Medical Institute; Estados Unidos
Fil: Goren, Alon. Massachusetts Institute of Technology; Estados Unidos
Fil: Rao, Anjana. La Jolla Institute for Allergy and Immunology; Estados Unidos. University of California at San Diego; Estados Unidos
Fil: Mostoslavsky, Raul. Harvard Medical School; Estados Unidos
description How embryonic stem cells (ESCs) commit to specific cell lineages and yield all cell types of a fully formed organism remains a major question. ESC differentiation is accompanied by large-scale histone and DNA modifications, but the relations between these epigenetic categories are not understood. Here we demonstrate the interplay between the histone deacetylase sirtuin 6 (SIRT6) and the ten-eleven translocation enzymes (TETs). SIRT6 targets acetylated histone H3 at Lys 9 and 56 (H3K9ac and H3K56ac), while TETs convert 5-methylcytosine into 5-hydroxymethylcytosine (5hmC). ESCs derived from Sirt6 knockout (S6KO) mice are skewed towards neuroectoderm development. This phenotype involves derepression of OCT4, SOX2 and NANOG, which causes an upregulation of TET-dependent production of 5hmC. Genome-wide analysis revealed neural genes marked with 5hmC in S6KO ESCs, thereby implicating TET enzymes in the neuroectoderm-skewed differentiation phenotype. We demonstrate that SIRT6 functions as a chromatin regulator safeguarding the balance between pluripotency and differentiation through Tet-mediated production of 5hmC.
publishDate 2015
dc.date.none.fl_str_mv 2015-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/45155
Etchegaray, Jean Pierre; Chavez, Lukas; Huang, Yun; Ross, Kenneth N.; Choi, Jiho; et al.; The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine; Nature Publishing Group; Nature Cell Biology; 17; 5; 5-2015; 545-557
1465-7392
CONICET Digital
CONICET
url http://hdl.handle.net/11336/45155
identifier_str_mv Etchegaray, Jean Pierre; Chavez, Lukas; Huang, Yun; Ross, Kenneth N.; Choi, Jiho; et al.; The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine; Nature Publishing Group; Nature Cell Biology; 17; 5; 5-2015; 545-557
1465-7392
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/ncb3147
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/ncb3147
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593707/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/vnd.openxmlformats-officedocument.wordprocessingml.document
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846781249371242496
score 12.982451

Publicaciones similares