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  Global delay in nascent strand DNA methylation

Charlton, J., Downing, T. L., Smith, Z. D., Gu, H., Clement, K., Pop, R., et al. (2018). Global delay in nascent strand DNA methylation. Nature Structural and Molecular Biology, 25(4), 327-332. doi:10.1038/s41594-018-0046-4.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-E264-0 Version Permalink: http://hdl.handle.net/21.11116/0000-0001-EED0-8
Genre: Journal Article

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Charlton, Jocelyn1, Author              
Downing, Timothy L. , Author
Smith, Zachary D. , Author
Gu, Hongcang, Author
Clement, Kendell , Author
Pop, Ramona, Author
Akopian, Veronika , Author
Klages, Sven2, Author              
Santos, David P. , Author
Tsankov, Alexander M. , Author
Timmermann, Bernd2, Author              
Ziller, Michael J. , Author
Kiskinis, Evangelos, Author
Gnirke, Andreas , Author
Meissner, Alexander1, Author              
Affiliations:
1Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2379694              
2Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              

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 Abstract: Cytosine methylation is widespread among organisms and essential for mammalian development. In line with early postulations of an epigenetic role in gene regulation, symmetric CpG methylation can be mitotically propagated over many generations with extraordinarily high fidelity. Here, we combine BrdU labeling and immunoprecipitation with genome-wide bisulfite sequencing to explore the inheritance of cytosine methylation onto newly replicated DNA in human cells. Globally, we observe a pronounced lag between the copying of genetic and epigenetic information in embryonic stem cells that is reconsolidated within hours to accomplish faithful mitotic transmission. Populations of arrested cells show a global reduction of lag-induced intermediate CpG methylation when compared to proliferating cells, whereas sites of transcription factor engagement appear cell-cycle invariant. Alternatively, the cancer cell line HCT116 preserves global epigenetic heterogeneity independently of cell-cycle arrest. Taken together, our data suggest that heterogeneous methylation largely reflects asynchronous proliferation, but is intrinsic to actively engaged cis-regulatory elements and cancer.

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Language(s): eng - English
 Dates: 2018-02-052018-03-122018-04
 Publication Status: Published in print
 Pages: 6
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 Rev. Method: -
 Identifiers: DOI: 10.1038/s41594-018-0046-4
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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: 25 (4) Sequence Number: - Start / End Page: 327 - 332 Identifier: ISSN: 1545-9993
CoNE: /journals/resource/954925603763