%0 Journal Article
%A Etchegaray, Jean-Pierre
%A Chavez, Lukas
%A Huang, Yun
%A Ross, Kenneth N
%A Choi, Jiho
%A Martinez-Pastor, Barbara
%A Walsh, Ryan M
%A Sommer, Cesar A
%A Lienhard, Matthias
%A Gladden, Adrianne
%A Kugel, Sita
%A Silberman, Dafne M
%A Ramaswamy, Sridhar
%A Mostoslavsky, Gustavo
%A Hochedlinger, Konrad
%A Goren, Alon
%A Rao, Anjana
%A Mostoslavsky, Raul
%T The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine.
%J Nature cell biology
%V 17
%N 5
%@ 1476-4679
%C New York, NY
%I Nature America
%M DKFZ-2017-02518
%P 545 - 557
%D 2015
%X 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.
%K DNA-Binding Proteins (NLM Chemicals)
%K Histones (NLM Chemicals)
%K Homeodomain Proteins (NLM Chemicals)
%K Nanog Homeobox Protein (NLM Chemicals)
%K Nanog protein, mouse (NLM Chemicals)
%K Octamer Transcription Factor-3 (NLM Chemicals)
%K Pou5f1 protein, mouse (NLM Chemicals)
%K Proto-Oncogene Proteins (NLM Chemicals)
%K SOXB1 Transcription Factors (NLM Chemicals)
%K Sox2 protein, mouse (NLM Chemicals)
%K TET1 protein, mouse (NLM Chemicals)
%K Tet2 protein, mouse (NLM Chemicals)
%K 5-hydroxymethylcytosine (NLM Chemicals)
%K Cytosine (NLM Chemicals)
%K Sirt6 protein, mouse (NLM Chemicals)
%K SIRT6 protein, human (NLM Chemicals)
%K Sirtuins (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:25915124
%2 pmc:PMC4593707
%R 10.1038/ncb3147
%U https://inrepo02.dkfz.de/record/126489