% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Yoo:120638,
      author       = {Y. Yoo and J. H. Park and C. Weigel$^*$ and D. B.
                      Liesenfeld and D. Weichenhan$^*$ and C. Plass$^*$ and D.-G.
                      Seo and A. M. Lindroth and Y. J. Park},
      title        = {{TET}-mediated hydroxymethylcytosine at the {P}parγ locus
                      is required for initiation of adipogenic differentiation.},
      journal      = {International journal of obesity and related metabolic
                      disorders},
      volume       = {41},
      number       = {4},
      issn         = {1476-5497},
      address      = {London [u.a.]},
      publisher    = {Nature Publ. Group56782},
      reportid     = {DKFZ-2017-01066},
      pages        = {652 - 659},
      year         = {2017},
      abstract     = {Adipose tissue is one of the main organs regulating energy
                      homeostasis via energy storage as well as endocrine
                      function. The adipocyte cell number is largely determined by
                      adipogenesis. While the molecular mechanism of adipogenesis
                      has been extensively studied, its role in dynamic DNA
                      methylation plasticity remains unclear. Recently, it has
                      been shown that Tet methylcytosine dioxygenase (TET) is
                      catalytically capable of oxidizing DNA 5-methylcytosine
                      (5-mC) to 5-hydroxymethylcytosine (5-hmC) toward a complete
                      removal of the methylated cytosine. We investigate whether
                      expression of the Tet genes and production of
                      hydroxymethylcytosine are required for preadipocyte
                      differentiation.Murine 3T3-L1 preadipocytes were used to
                      evaluate the role of Tet1 and Tet2 genes during
                      adipogenesis. Changes in adipogenic ability and in
                      epigenetic status were analyzed, with and without
                      interfering Tet1 and Tet2 expression using small interfering
                      RNA (siRNA). The adipogenesis was evaluated by Oil-Red-O
                      staining and induced expression of adipogenic genes using
                      quantitative polymerase chain reaction (qPCR). Levels of
                      5-hmC and 5-mC were measured by MassARRAY,
                      immunoprecipitation and GC mass spectrometry at specific
                      loci as well as globally.Both Tet1 and Tet2 genes were
                      upregulated in a time-dependent manner, accompanied by
                      increased expression of hallmark adipogenic genes such as
                      Pparγ and Fabp4 (P<0.05). The TET upregulation led to
                      reduced DNA methylation and elevated hydroxymethylcytosine,
                      both globally and specifically at the Pparγ locus (P<0.05
                      and P<0.01, respectively). Knockdown of Tet1 and Tet2
                      blocked adipogenesis (P<0.01) by repression of Pparγ
                      expression (P<0.05). In particular, Tet2 knockdown repressed
                      conversion of 5-mC to 5-hmC at the Pparγ locus (P<0.01).
                      Moreover, vitamin C treatment enhanced adipogenesis
                      (P<0.05), while fumarate treatment inhibited it (P<0.01) by
                      modulating TET activities.TET proteins, particularly TET2,
                      were required for adipogenesis by modulating DNA methylation
                      at the Pparγ locus, subsequently by inducing Pparγ gene
                      expression.},
      cin          = {C010},
      ddc          = {610},
      cid          = {I:(DE-He78)C010-20160331},
      pnm          = {322 - Genetics and Pathophysiology (POF3-322)},
      pid          = {G:(DE-HGF)POF3-322},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28100914},
      doi          = {10.1038/ijo.2017.8},
      url          = {https://inrepo02.dkfz.de/record/120638},
}