| Literature DB >> 24838012 |
Toni Pfaffeneder1, Fabio Spada1, Mirko Wagner1, Caterina Brandmayr2, Silvia K Laube2, David Eisen2, Matthias Truss3, Jessica Steinbacher2, Benjamin Hackner2, Olga Kotljarova2, David Schuermann4, Stylianos Michalakis5, Olesea Kosmatchev2, Stefan Schiesser2, Barbara Steigenberger2, Nada Raddaoui2, Gengo Kashiwazaki2, Udo Müller6, Cornelia G Spruijt7, Michiel Vermeulen8, Heinrich Leonhardt6, Primo Schär4, Markus Müller2, Thomas Carell2.
Abstract
Ten eleven translocation (Tet) enzymes oxidize the epigenetically important DNA base 5-methylcytosine (mC) stepwise to 5-hydroxymethylcytosine (hmC), 5-formylcytosine and 5-carboxycytosine. It is currently unknown whether Tet-induced oxidation is limited to cytosine-derived nucleobases or whether other nucleobases are oxidized as well. We synthesized isotopologs of all major oxidized pyrimidine and purine bases and performed quantitative MS to show that Tet-induced oxidation is not limited to mC but that thymine is also a substrate that gives 5-hydroxymethyluracil (hmU) in mouse embryonic stem cells (mESCs). Using MS-based isotope tracing, we show that deamination of hmC does not contribute to the steady-state levels of hmU in mESCs. Protein pull-down experiments in combination with peptide tracing identifies hmU as a base that influences binding of chromatin remodeling proteins and transcription factors, suggesting that hmU has a specific function in stem cells besides triggering DNA repair.Entities:
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Year: 2014 PMID： 24838012 DOI： 10.1038/nchembio.1532
Source DB: PubMed Journal: Nat Chem Biol ISSN： 1552-4450 Impact factor: 15.040