ORCID: https://orcid.org/0000-0001-7898-2831
(30. Januar 2020):
Analysis of an Active Deformylation Mechanism of 5-Formyldeoxycytidine (fdC) in Stem Cells.
In: Angewandte Chemie International Edition, Bd. 59, Nr. 14: S. 5591-5594
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Abstract
The removal of 5-methyl-deoxycytidine (mdC) from promoter elements is associated with reactivation of the silenced corresponding genes. It takes place through an active demethylation process involving the oxidation of mdC to 5-hydroxymethyl-deoxycytidine (hmdC) and further on to 5-formyl-deoxycytidine (fdC) and 5-carboxy-deoxycytidine (cadC) with the help of a-ketoglutarate-dependent Tet oxygenases. The next step can occur through the action of a glycosylase (TDG), which cleaves fdC out of the genome for replacement by dC. A second pathway is proposed to involve C-C bond cleavage that converts fdC directly into dC. A 6-aza-5-formyl-deoxycytidine (a-fdC) probe molecule was synthesized and fed to various somatic cell lines and induced mouse embryonic stem cells, together with a 2’-fluorinated fdC analogue (F-fdC). While deformylation of F-fdC was clearly observed in vivo, it did not occur with a-fdC, thus suggesting that the C-C bond-cleaving deformylation is initiated by nucleophilic activation.
| Dokumententyp: | Zeitschriftenartikel |
|---|---|
| EU Funded Grant Agreement Number: | 741912 |
| EU-Projekte: | Horizon 2020 > ERC Grants > ERC Advanced Grant > ERC Grant 741912: EPiR - The Chemical Basis of RNA Epigenetics |
| Publikationsform: | Publisher's Version |
| Keywords: | demethylation; DNA modifications; epigenetics; formylcytidine |
| Fakultät: | Chemie und Pharmazie > Department Chemie |
| Themengebiete: | 500 Naturwissenschaften und Mathematik > 540 Chemie |
| URN: | urn:nbn:de:bvb:19-epub-72516-1 |
| ISSN: | 1521-3773 |
| Sprache: | Englisch |
| Dokumenten ID: | 72516 |
| Datum der Veröffentlichung auf Open Access LMU: | 17. Jun. 2020, 08:15 |
| Letzte Änderungen: | 04. Nov. 2020, 13:53 |
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