Light-Activatable TET-Dioxygenases Reveal Dynamics of 5-Methylcytosine Oxidation and Transcriptome Reorganization

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dc.contributor.authorPalei, Shubhendu
dc.contributor.authorBuchmuller, Benjamin
dc.contributor.authorWolffgramm, Jan
dc.contributor.authorMuñoz-Lopez, Álvaro
dc.contributor.authorJung, Sascha
dc.contributor.authorCzodrowski, Paul
dc.contributor.authorSummerer, Daniel
dc.date.accessioned2020-09-18T10:00:09Z
dc.date.available2020-09-18T10:00:09Z
dc.date.issued2020-04-14
dc.description.abstractTen-eleven-translocation (TET) dioxygenases catalyze the oxidation of 5-methylcytosine (5mC), the central epigenetic regulator of mammalian DNA. This activity dynamically reshapes the epigenome and transcriptome by depositing oxidized 5mC derivatives and initiating active DNA demethylation. However, studying this dynamic is hampered by the inability to selectively activate individual TETs with temporal control in cells. We report activation of TETs in mammalian cells by incorporation of genetically encoded 4,5-dimethoxy-2-nitrobenzyl-l-serine as a transient active-site block, and its subsequent deprotection with light. Our approach 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 demethylation to chromatin and transcription regulation.en
dc.identifier.urihttp://hdl.handle.net/2003/39300
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-21201
dc.language.isoende
dc.subject.ddc570
dc.subject.ddc540
dc.titleLight-Activatable TET-Dioxygenases Reveal Dynamics of 5-Methylcytosine Oxidation and Transcriptome Reorganizationen
dc.typeTextde
dc.type.publicationtypereportde
dcterms.accessRightsopen access
eldorado.openaire.projectidentifierinfo:eu-repo/grantAgreement/EC/H2020/723863/EU/Programmable Readers, Writers, and Erasers of the Epigenetic Cytosine Code/EPICODEen
eldorado.secondarypublicationtruede
eldorado.secondarypublication.primaryidentifierhttps://doi.org/10.1021/jacs.0c01193de

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