Tet oxidizes thymine to 5-hydroxymethyluracil in mouse embryonic stem cell DNA

Pfaffeneder, T. and Spada, F. and Wagner, M. and Brandmayr, C. and Laube, S. K. and Eisen, D. and Truss, M. and Steinbacher, J. and Hackner, B. and Kotljarova, O. and Schuermann, D. and Michalakis, S. and Kosmatchev, O. and Schiesser, S. and Steigenberger, B. and Raddaoui, N. and Kashiwazaki, G. and Muller, U. and Spruijt, C. G. and Vermeulen, M. and Leonhardt, H. and Schar, P. and Muller, M. and Carell, T.. (2014) Tet oxidizes thymine to 5-hydroxymethyluracil in mouse embryonic stem cell DNA. Nature chemical biology, Vol. 10, H. 7. pp. 574-581.

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Official URL: http://edoc.unibas.ch/dok/A6338156

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Molecular Genetics (Schär)
UniBasel Contributors:Schär, Primo Leo
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Feb 2015 09:59
Deposited On:06 Feb 2015 09:59

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