Light-activatable TET-dioxygenases reveal dynamics of 5-Methylcytosine oxidation and transcriptome reorganization
| dc.contributor.author | Palei, Shubhendu | |
| dc.contributor.author | Buchmuller, Benjamin | |
| dc.contributor.author | Wolffgramm, Jan | |
| dc.contributor.author | Muñoz-Lopez, Álvaro | |
| dc.contributor.author | Jung, Sascha | |
| dc.contributor.author | Czodrowski, Paul | |
| dc.contributor.author | Summerer, Daniel | |
| dc.date.accessioned | 2022-07-15T09:21:25Z | |
| dc.date.available | 2022-07-15T09:21:25Z | |
| dc.date.issued | 2020-04-14 | |
| dc.description.abstract | Ten-eleven-translocation (TET) dioxygenases catalyze the oxidation of 5-methylcytosine (5mC), the central epigenetic regulator of mammalian DNA. This activity dy- namically reshapes epigenome and transcriptome by deposit- ing oxidized 5mC derivatives, and initiating active DNA de- methylation. However, studying this dynamic is hampered by the inability to selectively activate individual TETs with tem- poral control in cells. We report activation of TETs in mam- malian cells by incorporation of genetically encoded 4,5- dimethoxy-2-nitrobenzyl-L-serine as transient active site block, and its subsequent deprotection with light. Our ap- proach enables precise insights into the impact of cancer- associated TET2 mutations on the kinetics of TET2 catalysis in vivo, and allows time-resolved monitoring of target gene activation and transcriptome reorganization. This sets a basis for dissecting the order and kinetics of chromatin-associated events triggered by TET catalysis, ranging from DNA de- methylation to chromatin and transcription regulation. | de |
| dc.identifier.uri | http://hdl.handle.net/2003/40993 | |
| dc.identifier.uri | http://dx.doi.org/10.17877/DE290R-22842 | |
| dc.language.iso | en | de |
| dc.subject.ddc | 570 | |
| dc.subject.ddc | 540 | |
| dc.title | Light-activatable TET-dioxygenases reveal dynamics of 5-Methylcytosine oxidation and transcriptome reorganization | de |
| dc.type | Text | de |
| dc.type.publicationtype | article | de |
| eldorado.openaire.projectidentifier | info:eu-repo/grantAgreement/EC/H2020/723863/EU/Programmable Readers, Writers, and Erasers of the Epigenetic Cytosine Code/EPICODE | de |
| eldorado.secondarypublication | true | de |
| eldorado.secondarypublication.primarycitation | Journal of the American Chemical Society. 2020, 142, 16, 7289–7294 | de |
| eldorado.secondarypublication.primaryidentifier | https://doi.org/10.1021/jacs.0c01193 | de |