Home > Publications database > The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine. > print

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024 7 _ |a 10.1038/ncb3147
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024 7 _ |a 1465-7392
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024 7 _ |a 1476-4679
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037 _ _ |a DKFZ-2017-02518
041 _ _ |a eng
082 _ _ |a 570
100 1 _ |a Etchegaray, Jean-Pierre
|b 0
245 _ _ |a The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine.
260 _ _ |a New York, NY
|c 2015
|b Nature America
336 7 _ |a article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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.
536 _ _ |a 312 - Functional and structural genomics (POF3-312)
|0 G:(DE-HGF)POF3-312
|c POF3-312
|f POF III
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588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a DNA-Binding Proteins
|2 NLM Chemicals
650 _ 7 |a Histones
|2 NLM Chemicals
650 _ 7 |a Homeodomain Proteins
|2 NLM Chemicals
650 _ 7 |a Nanog Homeobox Protein
|2 NLM Chemicals
650 _ 7 |a Nanog protein, mouse
|2 NLM Chemicals
650 _ 7 |a Octamer Transcription Factor-3
|2 NLM Chemicals
650 _ 7 |a Pou5f1 protein, mouse
|2 NLM Chemicals
650 _ 7 |a Proto-Oncogene Proteins
|2 NLM Chemicals
650 _ 7 |a SOXB1 Transcription Factors
|2 NLM Chemicals
650 _ 7 |a Sox2 protein, mouse
|2 NLM Chemicals
650 _ 7 |a TET1 protein, mouse
|2 NLM Chemicals
650 _ 7 |a Tet2 protein, mouse
|2 NLM Chemicals
650 _ 7 |a 5-hydroxymethylcytosine
|0 1123-95-1
|2 NLM Chemicals
650 _ 7 |a Cytosine
|0 8J337D1HZY
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650 _ 7 |a Sirt6 protein, mouse
|0 EC 2.4.2.31
|2 NLM Chemicals
650 _ 7 |a SIRT6 protein, human
|0 EC 3.5.1.-
|2 NLM Chemicals
650 _ 7 |a Sirtuins
|0 EC 3.5.1.-
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700 1 _ |a Chavez, Lukas
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700 1 _ |a Huang, Yun
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700 1 _ |a Ross, Kenneth N
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700 1 _ |a Choi, Jiho
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700 1 _ |a Martinez-Pastor, Barbara
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700 1 _ |a Walsh, Ryan M
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700 1 _ |a Sommer, Cesar A
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700 1 _ |a Lienhard, Matthias
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700 1 _ |a Gladden, Adrianne
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700 1 _ |a Kugel, Sita
|b 10
700 1 _ |a Silberman, Dafne M
|b 11
700 1 _ |a Ramaswamy, Sridhar
|b 12
700 1 _ |a Mostoslavsky, Gustavo
|b 13
700 1 _ |a Hochedlinger, Konrad
|b 14
700 1 _ |a Goren, Alon
|b 15
700 1 _ |a Rao, Anjana
|b 16
700 1 _ |a Mostoslavsky, Raul
|b 17
773 _ _ |a 10.1038/ncb3147
|g Vol. 17, no. 5, p. 545 - 557
|0 PERI:(DE-600)1494945-3
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|t Nature cell biology
|v 17
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|x 1476-4679
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