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  Dnmt1 has de novo activity targeted to transposable elements

Haggerty, C., Kretzmer, H., Riemenschneider, C., Sampath Kumar, A., Mattei, A. L., Bailly, N., et al. (2021). Dnmt1 has de novo activity targeted to transposable elements. Nature Structural and Molecular Biology, 2021. doi:10.1038/s41594-021-00603-8.

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 Creators:
Haggerty, Chuck1, Author              
Kretzmer, Helene1, Author              
Riemenschneider, Christina1, Author              
Sampath Kumar, Abhishek1, Author              
Mattei, Alexandra L.1, Author              
Bailly, Nina1, Author              
Gottfreund, Judith , Author
Giesselmann, Pay1, Author              
Weigert, Raha1, Author              
Brändl, Björn1, Author              
Giehr, Pascal , Author
Buschow, Rene2, Author              
Galonska, Christina1, Author              
von Meyenn, Ferdinand , Author
Pappalardi, Melissa B. , Author
McCabe, Michael T. , Author
Wittler, Lars3, Author              
Giesecke-Thiel, Claudia4, Author              
Mielke, Thorsten2, Author              
Meierhofer, David5, Author              
Timmermann, Bernd6, Author              Müller, Franz-Josef7, Author              Walter, Jörn, AuthorMeissner, Alexander1, Author               more..
Affiliations:
1Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2379694              
2Microscopy and Cryo-Electron Microscopy (Head: Thorsten Mielke), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479668              
3Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433548              
4Flow Cytometry Facility (Head: Claudia Giesecke-Thiel), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_3039333              
5Mass Spectrometry (Head: David Meierhofer), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479669              
6Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              
7Cellular Phenotyping (Franz-Josef Müller), Dept. of Genome Regulation, (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_3014190              

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 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.

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Language(s): eng - English
 Dates: 2021-05-102021-06-17
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1038/s41594-021-00603-8
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Title: Nature Structural and Molecular Biology
  Other : Nature Struct Biol
Source Genre: Journal
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Publ. Info: New York, NY : Nature Pub. Group
Pages: - Volume / Issue: 2021 Sequence Number: - Start / End Page: - Identifier: ISSN: 1545-9993
CoNE: https://pure.mpg.de/cone/journals/resource/954925603763