2026-05-17T01:18:32Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/262172025-12-18T12:54:25Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Etchegaray, Jean-Pierre
author
Chavez, Lukas
author
Huang, Yun
author
Ross, Kenneth N
author
Choi, Jiho
author
Martinez-Pastor, Barbara
author
Walsh, Ryan M
author
Sommer, Cesar A
author
Lienhard, Matthias
author
Gladden, Adrianne
author
Kugel, Sita
author
Silberman, Dafne M
author
Ramaswamy, Sridhar
author
Mostoslavsky, Gustavo
author
Hochedlinger, Konrad
author
Goren, Alon
author
Rao, Anjana
author
Mostoslavsky, Raul
2025-01-31T11:53:35Z
2025-01-31T11:53:35Z
2015-05
https://pmc.ncbi.nlm.nih.gov/articles/PMC4593707/pdf/nihms725229.pdf
25915124
https://hdl.handle.net/20.500.12105/26217
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.
eng
The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine.
research article
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URL
https://repisalud.isciii.es/bitstreams/602932cf-f934-4258-b653-65092c9969dd/download
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4a5be6532be082928a8b70d90af42b15
1615958
application/pdf
thehistonedeacetylase-2015.pdf