We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Tet oxidizes thymine to 5-hydroxymethyluracil in mouse embryonic stem cell DNA.
- Authors
Pfaffeneder, Toni; Spada, Fabio; Wagner, Mirko; Brandmayr, Caterina; Laube, Silvia K; Eisen, David; Truss, Matthias; Steinbacher, Jessica; Hackner, Benjamin; Kotljarova, Olga; Schuermann, David; Michalakis, Stylianos; Kosmatchev, Olesea; Schiesser, Stefan; Steigenberger, Barbara; Raddaoui, Nada; Kashiwazaki, Gengo; Müller, Udo; Spruijt, Cornelia G; Vermeulen, Michiel
- 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.
- Subjects
EMBRYONIC stem cell research; CHROMOSOMAL translocation; METHYLCYTOSINE; DNA repair; TRANSCRIPTION factors; DEAMINATION; THYMINE
- Publication
Nature Chemical Biology, 2014, Vol 10, Issue 7, p574
- ISSN
1552-4450
- Publication type
Article
- DOI
10.1038/nchembio.1532