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

Publication type:
Journal article
Metadata:
Autoren
  • Shubhendu Palei
  • Benjamin Buchmuller
  • Jan Wolffgramm
  • Alvaro Munoz-Lopez
  • Sascha Jung
  • Paul Czodrowski
  • Daniel Summerer
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000529156100009&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1021/jacs.0c01193
eISSN
1520-5126
Externe Identifier
  • Clarivate Analytics Document Solution ID: LI0DX
  • PubMed Identifier: 32286069
ISSN
0002-7863
Ausgabe der Veröffentlichung
16
Zeitschrift
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Paginierung
7289 - 7294
Datum der Veröffentlichung
2020
Status
Published
Titel
Light-Activatable TET-Dioxygenases Reveal Dynamics of 5-Methylcytosine Oxidation and Transcriptome Reorganization
Sub types
  • Article
Ausgabe der Zeitschrift
142

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Shubhendu Palei
  • Benjamin Buchmuller
  • Jan Wolffgramm
  • Álvaro Muñoz-Lopez
  • Sascha Jung
  • Paul Czodrowski
  • Daniel Summerer
DOI
10.1021/jacs.0c01193
eISSN
1520-5126
ISSN
0002-7863
Ausgabe der Veröffentlichung
16
Zeitschrift
Journal of the American Chemical Society
Sprache
en
Online publication date
2020
Paginierung
7289 - 7294
Datum der Veröffentlichung
2020
Status
Published
Herausgeber
American Chemical Society (ACS)
Herausgeber URL
http://dx.doi.org/10.1021/jacs.0c01193
Datum der Datenerfassung
2023
Titel
Light-Activatable TET-Dioxygenases Reveal Dynamics of 5-Methylcytosine Oxidation and Transcriptome Reorganization
Ausgabe der Zeitschrift
142

Data source: Crossref

Abstract
Ten-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 <i>in vivo</i>, 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.
Addresses
  • Faculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Straße 6, 44227 Dortmund, Germany.
Autoren
  • Shubhendu Palei
  • Benjamin Buchmuller
  • Jan Wolffgramm
  • Álvaro Muñoz-Lopez
  • Sascha Jung
  • Paul Czodrowski
  • Daniel Summerer
DOI
10.1021/jacs.0c01193
eISSN
1520-5126
Externe Identifier
  • PubMed Identifier: 32286069
Funding acknowledgements
  • European Research Council: EPICODE
Open access
false
ISSN
0002-7863
Ausgabe der Veröffentlichung
16
Zeitschrift
Journal of the American Chemical Society
Schlüsselwörter
  • Humans
  • 5-Methylcytosine
  • Dioxygenases
  • Oxidation-Reduction
  • Transcriptome
Sprache
eng
Medium
Print-Electronic
Online publication date
2020
Paginierung
7289 - 7294
Datum der Veröffentlichung
2020
Status
Published
Datum der Datenerfassung
2020
Titel
Light-Activatable TET-Dioxygenases Reveal Dynamics of 5-Methylcytosine Oxidation and Transcriptome Reorganization.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
142

Data source: Europe PubMed Central

Abstract
Ten-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.
Autoren
  • Shubhendu Palei
  • Benjamin Buchmuller
  • Jan Wolffgramm
  • Álvaro Muñoz-Lopez
  • Sascha Jung
  • Paul Czodrowski
  • Daniel Summerer
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/32286069
DOI
10.1021/jacs.0c01193
eISSN
1520-5126
Ausgabe der Veröffentlichung
16
Zeitschrift
J Am Chem Soc
Schlüsselwörter
  • 5-Methylcytosine
  • Dioxygenases
  • Humans
  • Oxidation-Reduction
  • Transcriptome
Sprache
eng
Country
United States
Paginierung
7289 - 7294
Datum der Veröffentlichung
2020
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2021
Titel
Light-Activatable TET-Dioxygenases Reveal Dynamics of 5-Methylcytosine Oxidation and Transcriptome Reorganization.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
142

Data source: PubMed

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