Science (American Association for the Advancement of Science), 2011-09, Vol.333 (6047), p.1303-1307
2011
Details
- Autor(en) / Beteiligte
- Titel
- Tet-Mediated Formation of 5-Carboxylcytosine and Its Excision by TDG in Mammalian DNA
- Ist Teil von
- Science (American Association for the Advancement of Science), 2011-09, Vol.333 (6047), p.1303-1307
- Ort / Verlag
- Washington, DC: American Association for the Advancement of Science
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- American Association for the Advancement of Science
- Beschreibungen/Notizen
- The prevalent DNA modification in higher organisms is the methylation of cytosine to 5-methylcytosine (5mC), which is partially converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) family of dioxygenases. Despite their importance in epigenetic regulation, it is unclear how these cytosine modifications are reversed. Here, we demonstrate that 5mC and 5hmC in DNA are oxidized to 5-carboxylcytosine (5caC) by Tet dioxygenases in vitro and in cultured cells. 5caC is specifically recognized and excised by thymine-DNA glycosylase (TDG). Depletion of TDG in mouse embyronic stem cells leads to accumulation of 5caC to a readily detectable level. These data suggest that oxidation of 5mC by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.1210944Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3462231
- Format
- –
- Schlagworte
- 5-Methylcytosine - metabolism, Animals, Biological and medical sciences, Cell Line, Cell lines, Cell nucleus, Cytosine, Cytosine - analogs & derivatives, Cytosine - metabolism, DNA, DNA - metabolism, DNA Methylation, DNA repair, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, Embryonic Stem Cells, Enzymes, Fundamental and applied biological sciences. Psychology, Genomics, Glycosylation, HEK293 Cells, Humans, Induced pluripotent stem cells, Induced Pluripotent Stem Cells - metabolism, Mammals, Mice, Molecular and cellular biology, Molecular genetics, Nucleosides, Nucleotides, Oxidation, Oxidation-Reduction, Proto-Oncogene Proteins - genetics, Proto-Oncogene Proteins - metabolism, RNA, Small Interfering, Stem cells, Thymine DNA Glycosylase - genetics, Thymine DNA Glycosylase - metabolism, Transcription. Transcription factor. Splicing. Rna processing, Transfection