Details

Autor(en) / Beteiligte

• 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
• Leonhardt, Heinrich
• Schär, Primo
• Müller, Markus
• Carell, Thomas

Titel

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

Ist Teil von

• Nature chemical biology, 2014-07, Vol.10 (7), p.574-581

Ort / Verlag

United States

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.