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  Targets and genomic constraints of ectopic Dnmt3b expression

Zhang, Y., Charlton, J., Karnik, R., Beerman, I., Smith, Z. D., Gu, H., et al. (2018). Targets and genomic constraints of ectopic Dnmt3b expression. eLife, 7: e40757. doi:10.7554/eLife.40757.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-60E5-E Version Permalink: http://hdl.handle.net/21.11116/0000-0003-60E6-D
Genre: Journal Article

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 Creators:
Zhang, Yingying , Author
Charlton, Jocelyn1, Author              
Karnik, Rahul , Author
Beerman, Isabel , Author
Smith, Zachary D., Author
Gu, Hongcang , Author
Boyle, Patrick , Author
Mi , Xiaoli , Author
Clement, Kendell , Author
Pop, Ramona, Author
Gnirke, Andreas , Author
Rossi, Derrick J. , Author
Meissner, Alexander1, 2, 3, Author              
Affiliations:
1Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2379694              
2Department of Stem Cell and Regenerative Biology, Harvard University, Massachusetts, United States, ou_persistent22              
3Broad Institute of MIT and Harvard, Massachusetts, United States, ou_persistent22              

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Free keywords: MEFs; blood; cancer biology; genetics; genomics; human; liver; mouse; stem cells
 Abstract: DNA methylation plays an essential role in mammalian genomes and expression of the responsible enzymes is tightly controlled. Deregulation of the de novo DNA methyltransferase DNMT3B is frequently observed across cancer types, yet little is known about its ectopic genomic targets. Here, we used an inducible transgenic mouse model to delineate rules for abnormal DNMT3B targeting, as well as the constraints of its activity across different cell types. Our results explain the preferential susceptibility of certain CpG islands to aberrant methylation and point to transcriptional state and the associated chromatin landscape as the strongest predictors. Although DNA methylation and H3K27me3 are usually non-overlapping at CpG islands, H3K27me3 can transiently co-occur with DNMT3B-induced DNA methylation. Our genome-wide data combined with ultra-deep locus-specific bisulfite sequencing suggest a distributive activity of ectopically expressed Dnmt3b that leads to discordant CpG island hypermethylation and provides new insights for interpreting the cancer methylome.

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Language(s): eng - English
 Dates: 2018-11-092018-11-23
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.7554/eLife.40757
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Title: eLife
Source Genre: Journal
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Publ. Info: Cambridge : eLife Sciences Publications
Pages: - Volume / Issue: 7 Sequence Number: e40757 Start / End Page: - Identifier: ISSN: 2050-084X
CoNE: https://pure.mpg.de/cone/journals/resource/2050-084X