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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/45155
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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 Técnicas2025-09-29T09:34:53Zoai: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:34982025-09-29 09:34:54.161CONICET 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 |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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13.070432 |