Pronounced sequence specificity of the TET enzyme catalytic domain guides its cellular function
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Mirunalini Ravichandran
- Dominik Rafalski
- Claudia I Davies
- Oscar Ortega-Recalde
- Xinsheng Nan
- Cassandra R Glanfield
- Annika Kotter
- Katarzyna Misztal
- Andrew H Wang
- Marek Wojciechowski
- Michal Razew
- Issam M Mayyas
- Olga Kardailsky
- Uwe Schwartz
- Krzysztof Zembrzycki
- Ian M Morison
- Mark Helm
- Dieter Weichenhan
- Renata Z Jurkowska
- Felix Krueger
- Christoph Plass
- Martin Zacharias
- Matthias Bochtler
- Timothy A Hore
- Tomasz P Jurkowski
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000911968500003&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1126/sciadv.abm2427
- Externe Identifier
- Clarivate Analytics Document Solution ID: 7U2MI
- PubMed Identifier: 36070377
- ISSN
- 2375-2548
- Ausgabe der Veröffentlichung
- 36
- Zeitschrift
- SCIENCE ADVANCES
- Artikelnummer
- ARTN eabm2427
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Titel
- Pronounced sequence specificity of the TET enzyme catalytic domain guides its cellular function
- Sub types
- Article
- Ausgabe der Zeitschrift
- 8
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Abstract
- <jats:p>TET (ten-eleven translocation) enzymes catalyze the oxidation of 5-methylcytosine bases in DNA, thus driving active and passive DNA demethylation. Here, we report that the catalytic domain of mammalian TET enzymes favor CGs embedded within basic helix-loop-helix and basic leucine zipper domain transcription factor–binding sites, with up to 250-fold preference in vitro. Crystal structures and molecular dynamics calculations show that sequence preference is caused by intrasubstrate interactions and CG flanking sequence indirectly affecting enzyme conformation. TET sequence preferences are physiologically relevant as they explain the rates of DNA demethylation in TET-rescue experiments in culture and in vivo within the zygote and germ line. Most and least favorable TET motifs represent DNA sites that are bound by methylation-sensitive immediate-early transcription factors and octamer-binding transcription factor 4 (OCT4), respectively, illuminating TET function in transcriptional responses and pluripotency support.</jats:p>
- Autoren
- Mirunalini Ravichandran
- Dominik Rafalski
- Claudia I Davies
- Oscar Ortega-Recalde
- Xinsheng Nan
- Cassandra R Glanfield
- Annika Kotter
- Katarzyna Misztal
- Andrew H Wang
- Marek Wojciechowski
- Michał Rażew
- Issam M Mayyas
- Olga Kardailsky
- Uwe Schwartz
- Krzysztof Zembrzycki
- Ian M Morison
- Mark Helm
- Dieter Weichenhan
- Renata Z Jurkowska
- Felix Krueger
- Christoph Plass
- Martin Zacharias
- Matthias Bochtler
- Timothy A Hore
- Tomasz P Jurkowski
- DOI
- 10.1126/sciadv.abm2427
- eISSN
- 2375-2548
- Ausgabe der Veröffentlichung
- 36
- Zeitschrift
- Science Advances
- Sprache
- en
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Herausgeber
- American Association for the Advancement of Science (AAAS)
- Herausgeber URL
- http://dx.doi.org/10.1126/sciadv.abm2427
- Datum der Datenerfassung
- 2024
- Titel
- Pronounced sequence specificity of the TET enzyme catalytic domain guides its cellular function
- Ausgabe der Zeitschrift
- 8
Datenquelle: Crossref
- Abstract
- TET (ten-eleven translocation) enzymes catalyze the oxidation of 5-methylcytosine bases in DNA, thus driving active and passive DNA demethylation. Here, we report that the catalytic domain of mammalian TET enzymes favor CGs embedded within basic helix-loop-helix and basic leucine zipper domain transcription factor-binding sites, with up to 250-fold preference in vitro. Crystal structures and molecular dynamics calculations show that sequence preference is caused by intrasubstrate interactions and CG flanking sequence indirectly affecting enzyme conformation. TET sequence preferences are physiologically relevant as they explain the rates of DNA demethylation in TET-rescue experiments in culture and in vivo within the zygote and germ line. Most and least favorable TET motifs represent DNA sites that are bound by methylation-sensitive immediate-early transcription factors and octamer-binding transcription factor 4 (OCT4), respectively, illuminating TET function in transcriptional responses and pluripotency support.
- Addresses
- Department of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, HSW 1301, San Francisco, CA 94143, USA.
- Autoren
- Mirunalini Ravichandran
- Dominik Rafalski
- Claudia I Davies
- Oscar Ortega-Recalde
- Xinsheng Nan
- Cassandra R Glanfield
- Annika Kotter
- Katarzyna Misztal
- Andrew H Wang
- Marek Wojciechowski
- Michał Rażew
- Issam M Mayyas
- Olga Kardailsky
- Uwe Schwartz
- Krzysztof Zembrzycki
- Ian M Morison
- Mark Helm
- Dieter Weichenhan
- Renata Z Jurkowska
- Felix Krueger
- Christoph Plass
- Martin Zacharias
- Matthias Bochtler
- Timothy A Hore
- Tomasz P Jurkowski
- DOI
- 10.1126/sciadv.abm2427
- eISSN
- 2375-2548
- Externe Identifier
- PubMed Identifier: 36070377
- PubMed Central ID: PMC9451156
- Open access
- true
- ISSN
- 2375-2548
- Ausgabe der Veröffentlichung
- 36
- Zeitschrift
- Science advances
- Schlüsselwörter
- Animals
- Mammals
- 5-Methylcytosine
- Dioxygenases
- DNA
- Catalytic Domain
- Cell Physiological Phenomena
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2022
- Open access status
- Open Access
- Paginierung
- eabm2427
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Publisher licence
- CC BY-NC
- Datum der Datenerfassung
- 2022
- Titel
- Pronounced sequence specificity of the TET enzyme catalytic domain guides its cellular function.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 8
Files
https://bib-pubdb1.desy.de/record/491473/files/2022_ravichandran.pdf https://europepmc.org/articles/PMC9451156?pdf=render
Datenquelle: Europe PubMed Central
- Abstract
- TET (ten-eleven translocation) enzymes catalyze the oxidation of 5-methylcytosine bases in DNA, thus driving active and passive DNA demethylation. Here, we report that the catalytic domain of mammalian TET enzymes favor CGs embedded within basic helix-loop-helix and basic leucine zipper domain transcription factor-binding sites, with up to 250-fold preference in vitro. Crystal structures and molecular dynamics calculations show that sequence preference is caused by intrasubstrate interactions and CG flanking sequence indirectly affecting enzyme conformation. TET sequence preferences are physiologically relevant as they explain the rates of DNA demethylation in TET-rescue experiments in culture and in vivo within the zygote and germ line. Most and least favorable TET motifs represent DNA sites that are bound by methylation-sensitive immediate-early transcription factors and octamer-binding transcription factor 4 (OCT4), respectively, illuminating TET function in transcriptional responses and pluripotency support.
- Autoren
- Mirunalini Ravichandran
- Dominik Rafalski
- Claudia I Davies
- Oscar Ortega-Recalde
- Xinsheng Nan
- Cassandra R Glanfield
- Annika Kotter
- Katarzyna Misztal
- Andrew H Wang
- Marek Wojciechowski
- Michał Rażew
- Issam M Mayyas
- Olga Kardailsky
- Uwe Schwartz
- Krzysztof Zembrzycki
- Ian M Morison
- Mark Helm
- Dieter Weichenhan
- Renata Z Jurkowska
- Felix Krueger
- Christoph Plass
- Martin Zacharias
- Matthias Bochtler
- Timothy A Hore
- Tomasz P Jurkowski
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/36070377
- DOI
- 10.1126/sciadv.abm2427
- eISSN
- 2375-2548
- Externe Identifier
- PubMed Central ID: PMC9451156
- Ausgabe der Veröffentlichung
- 36
- Zeitschrift
- Sci Adv
- Schlüsselwörter
- 5-Methylcytosine
- Animals
- Catalytic Domain
- Cell Physiological Phenomena
- DNA
- Dioxygenases
- Mammals
- Sprache
- eng
- Country
- United States
- Paginierung
- eabm2427
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2022
- Titel
- Pronounced sequence specificity of the TET enzyme catalytic domain guides its cellular function.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 8
Datenquelle: PubMed
- Beziehungen:
- Eigentum von