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@ARTICLE{Kang:126813,
      author       = {J. Kang and M. Lienhard and W. A. Pastor and A. Chawla and
                      M. Novotny and A. Tsagaratou and R. S. Lasken and E. C.
                      Thompson and M. A. Surani and S. B. Koralov and S. Kalantry
                      and L. Chavez$^*$ and A. Rao},
      title        = {{S}imultaneous deletion of the methylcytosine oxidases
                      {T}et1 and {T}et3 increases transcriptome variability in
                      early embryogenesis.},
      journal      = {Proceedings of the National Academy of Sciences of the
                      United States of America},
      volume       = {112},
      number       = {31},
      issn         = {1091-6490},
      address      = {Washington, DC},
      publisher    = {National Acad. of Sciences},
      reportid     = {DKFZ-2017-02841},
      pages        = {E4236 - E4245},
      year         = {2015},
      abstract     = {Dioxygenases of the TET (Ten-Eleven Translocation) family
                      produce oxidized methylcytosines, intermediates in DNA
                      demethylation, as well as new epigenetic marks. Here we show
                      data suggesting that TET proteins maintain the consistency
                      of gene transcription. Embryos lacking Tet1 and Tet3 (Tet1/3
                      DKO) displayed a strong loss of 5-hydroxymethylcytosine
                      (5hmC) and a concurrent increase in 5-methylcytosine (5mC)
                      at the eight-cell stage. Single cells from eight-cell
                      embryos and individual embryonic day 3.5 blastocysts showed
                      unexpectedly variable gene expression compared with
                      controls, and this variability correlated in blastocysts
                      with variably increased 5mC/5hmC in gene bodies and
                      repetitive elements. Despite the variability, genes encoding
                      regulators of cholesterol biosynthesis were reproducibly
                      down-regulated in Tet1/3 DKO blastocysts, resulting in a
                      characteristic phenotype of holoprosencephaly in the few
                      embryos that survived to later stages. Thus, TET enzymes and
                      DNA cytosine modifications could directly or indirectly
                      modulate transcriptional noise, resulting in the selective
                      susceptibility of certain intracellular pathways to
                      regulation by TET proteins.},
      keywords     = {Biomarkers (NLM Chemicals) / DNA-Binding Proteins (NLM
                      Chemicals) / Hedgehog Proteins (NLM Chemicals) /
                      Proto-Oncogene Proteins (NLM Chemicals) / Shh protein, mouse
                      (NLM Chemicals) / TET1 protein, mouse (NLM Chemicals) / Tet3
                      protein, mouse (NLM Chemicals) / 5-Methylcytosine (NLM
                      Chemicals) / DNA (NLM Chemicals) / Cholesterol (NLM
                      Chemicals)},
      cin          = {B062},
      ddc          = {000},
      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:26199412},
      pmc          = {pmc:PMC4534209},
      doi          = {10.1073/pnas.1510510112},
      url          = {https://inrepo02.dkfz.de/record/126813},
}