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dc.contributor.author
Haggerty, Chuck
dc.contributor.author
Kretzmer, Helene
dc.contributor.author
Riemenschneider, Christina
dc.contributor.author
Kumar, Abhishek Sampath
dc.contributor.author
Mattei, Alexandra L.
dc.contributor.author
Bailly, Nina
dc.contributor.author
Gottfreund, Judith
dc.contributor.author
Giesselmann, Pay
dc.contributor.author
Weigert, Raha
dc.contributor.author
Brändl, Björn
dc.contributor.author
Giehr, Pascal
dc.contributor.author
Buschow, René
dc.contributor.author
Galonska, Christina
dc.contributor.author
von Meyenn, Ferdinand
dc.contributor.author
Pappalardi, Melissa B.
dc.contributor.author
McCabe, Michael T.
dc.contributor.author
Wittler, Lars
dc.contributor.author
Giesecke-Thiel, Claudia
dc.contributor.author
Mielke, Thorsten
dc.contributor.author
Meierhofer, David
dc.contributor.author
Timmermann, Bernd
dc.contributor.author
Müller, Franz-Josef
dc.contributor.author
Walter, Jörn
dc.contributor.author
Meissner, Alexander
dc.date.accessioned
2021-07-23T07:11:53Z
dc.date.available
2021-07-06T05:35:42Z
dc.date.available
2021-07-23T07:11:53Z
dc.date.issued
2021-07
dc.identifier.issn
1545-9993
dc.identifier.issn
1545-9985
dc.identifier.other
10.1038/s41594-021-00603-8
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/493189
dc.identifier.doi
10.3929/ethz-b-000493189
dc.description.abstract
DNA methylation plays a critical role during development, particularly in repressing retrotransposons. The mammalian methylation landscape is dependent on the combined activities of the canonical maintenance enzyme Dnmt1 and the de novo Dnmts, 3a and 3b. Here, we demonstrate that Dnmt1 displays de novo methylation activity in vitro and in vivo with specific retrotransposon targeting. We used whole-genome bisulfite and long-read Nanopore sequencing in genetically engineered methylation-depleted mouse embryonic stem cells to provide an in-depth assessment and quantification of this activity. Utilizing additional knockout lines and molecular characterization, we show that the de novo methylation activity of Dnmt1 depends on Uhrf1, and its genomic recruitment overlaps with regions that enrich for Uhrf1, Trim28 and H3K9 trimethylation. Our data demonstrate that Dnmt1 can catalyze DNA methylation in both a de novo and maintenance context, especially at retrotransposons, where this mechanism may provide additional stability for long-term repression and epigenetic propagation throughout development.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Nature Publishing Group
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Chromatin
en_US
dc.subject
Developmental biology
en_US
dc.subject
DNA methylation
en_US
dc.subject
Epigenomics
en_US
dc.title
Dnmt1 has de novo activity targeted to transposable elements
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2021-06-17
ethz.journal.title
Nature Structural & Molecular Biology
ethz.journal.volume
28
en_US
ethz.journal.issue
7
en_US
ethz.journal.abbreviated
Struct. Mol. Biol.
ethz.pages.start
594
en_US
ethz.pages.end
603
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02701 - Inst.f. Lebensmittelwiss.,Ernährung,Ges. / Institute of Food, Nutrition, and Health::09658 - von Meyenn, Ferdinand / von Meyenn, Ferdinand
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02701 - Inst.f. Lebensmittelwiss.,Ernährung,Ges. / Institute of Food, Nutrition, and Health::09658 - von Meyenn, Ferdinand / von Meyenn, Ferdinand
en_US
ethz.date.deposited
2021-06-22T15:02:06Z
ethz.source
FORM
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2021-07-23T07:11:59Z
ethz.rosetta.lastUpdated
2021-07-23T07:11:59Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
dc.identifier.olduri
http://hdl.handle.net/20.500.11850/490786
dc.identifier.olduri
http://hdl.handle.net/20.500.11850/492968
ethz.COinS
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