Dnmt1 has de novo activity targeted to transposable elements
| Autor: | David Meierhofer, Raha Weigert, Nina Bailly, Claudia Giesecke-Thiel, Judith Gottfreund, Chuck Haggerty, Alexander Meissner, Jörn Walter, Christina Galonska, Abhishek Sampath Kumar, Thorsten Mielke, Franz-Josef Müller, Björn Brändl, Pascal Giehr, Helene Kretzmer, Bernd Timmermann, Lars Wittler, Ferdinand von Meyenn, René Buschow, Christina Riemenschneider, Alexandra L. Mattei, Melissa B. Pappalardi, Pay Giesselmann, Michael T. McCabe |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
DNA (Cytosine-5-)-Methyltransferase 1
Transposable element Epigenomics Ubiquitin-Protein Ligases Embryonic Development Retrotransposon Tripartite Motif-Containing Protein 28 Biology Article DNA Methyltransferase 3A Histones Gene Knockout Techniques Mice Structural Biology Developmental biology Animals DNA (Cytosine-5-)-Methyltransferases Epigenetics Molecular Biology Chromatin DNA methylation Cells Cultured Genome Whole Genome Sequencing Mouse Embryonic Stem Cells 500 Naturwissenschaften und Mathematik::570 Biowissenschaften Biologie::570 Biowissenschaften Biologie Methylation Cell biology CCAAT-Enhancer-Binding Proteins DNA Transposable Elements DNMT1 |
| Zdroj: | Nature Structural and Molecular Biology Nature Structural & Molecular Biology Nature Structural & Molecular Biology, 28 (7) |
| ISSN: | 1545-9993 1545-9985 |
| DOI: | 10.3929/ethz-b-000493189 |
| Popis: | 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. Nature Structural & Molecular Biology, 28 (7) ISSN:1545-9993 ISSN:1545-9985 |
| Databáze: | OpenAIRE |
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