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@ARTICLE{Etchegaray:126489,
      author       = {J.-P. Etchegaray and L. Chavez$^*$ and Y. Huang and K. N.
                      Ross and J. Choi and B. Martinez-Pastor and R. M. Walsh and
                      C. A. Sommer and M. Lienhard and A. Gladden and S. Kugel and
                      D. M. Silberman and S. Ramaswamy and G. Mostoslavsky and K.
                      Hochedlinger and A. Goren and A. Rao and R. Mostoslavsky},
      title        = {{T}he histone deacetylase {SIRT}6 controls embryonic stem
                      cell fate via {TET}-mediated production of
                      5-hydroxymethylcytosine.},
      journal      = {Nature cell biology},
      volume       = {17},
      number       = {5},
      issn         = {1476-4679},
      address      = {New York, NY},
      publisher    = {Nature America},
      reportid     = {DKFZ-2017-02518},
      pages        = {545 - 557},
      year         = {2015},
      abstract     = {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.},
      keywords     = {DNA-Binding Proteins (NLM Chemicals) / Histones (NLM
                      Chemicals) / Homeodomain Proteins (NLM Chemicals) / Nanog
                      Homeobox Protein (NLM Chemicals) / Nanog protein, mouse (NLM
                      Chemicals) / Octamer Transcription Factor-3 (NLM Chemicals)
                      / Pou5f1 protein, mouse (NLM Chemicals) / Proto-Oncogene
                      Proteins (NLM Chemicals) / SOXB1 Transcription Factors (NLM
                      Chemicals) / Sox2 protein, mouse (NLM Chemicals) / TET1
                      protein, mouse (NLM Chemicals) / Tet2 protein, mouse (NLM
                      Chemicals) / 5-hydroxymethylcytosine (NLM Chemicals) /
                      Cytosine (NLM Chemicals) / Sirt6 protein, mouse (NLM
                      Chemicals) / SIRT6 protein, human (NLM Chemicals) / Sirtuins
                      (NLM Chemicals)},
      cin          = {B062},
      ddc          = {570},
      cid          = {I:(DE-He78)B062-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:25915124},
      pmc          = {pmc:PMC4593707},
      doi          = {10.1038/ncb3147},
      url          = {https://inrepo02.dkfz.de/record/126489},
}