The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
Targeted disruption of DNMT1, DNMT3A and DNMT3B in human embryonic stem cells
Open accessAbstract
DNA methylation is a key epigenetic modification involved in regulating gene expression and maintaining genomic integrity. Here we inactivated all three catalytically active DNA methyltransferases (DNMTs) in human embryonic stem cells (ESCs) using CRISPR/Cas9 genome editing to further investigate the roles and genomic targets of these enzymes. Disruption of DNMT3A or DNMT3B individually as well as of both enzymes in tandem results in viable, pluripotent cell lines with distinct effects on the DNA methylation landscape, as assessed by whole-genome bisulfite sequencing. Surprisingly, in contrast to findings in mouse, deletion of DNMT1 resulted in rapid cell death in human ESCs. To overcome this immediate lethality, we generated a doxycycline-responsive tTA-DNMT1* rescue line and readily obtained homozygous DNMT1-mutant lines. However, doxycycline-mediated repression of exogenous DNMT1* initiates rapid, global loss of DNA methylation, followed by extensive cell death. Our data provide a comprehensive characterization of DNMT-mutant ESCs, including single-base genome-wide maps of the targets of these enzymes.
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Citations
Cites
Multiplex Genome Engineering Using CRISPR/Cas Systems
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Cited by
Dynamic stem cell states: Naive to primed pluripotency in rodents and humans
Weinberger, L., Ayyash, M., Novershtern, N., & Hanna, J. H. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2015.28 · Cited by 622
Pluripotent stem cells in disease modelling and drug discovery
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Induced Pluripotent Stem Cells Meet Genome Editing
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“…(Chen et al., 2015; Cong et al., 2013; Fu et al., 2014; Gonzalez et al., 2014; Gu et al., 2015; Hou et al., 2013; Hsu et al., 2014; Kleinstiver et al., 2016; Liao and Karnik, 2015; Lin et al., 2014; Mali et al., 2013; Ran et al., 2015; Slaymaker et al., 2016; Tsai et al., 2014; Wu et al., 2014b).”
BackgroundEditing the epigenome: technologies for programmable transcription and epigenetic modulation
Thakore, P. I., Black, J. B., Hilton, I. B., & Gersbach, C. A. (2016) · Nature Methods · doi:10.1038/nmeth.3733 · Cited by 451
CpG and non-CpG methylation in epigenetic gene regulation and brain function
Jang, H., Shin, W., Lee, J., & Do, J. (2017) · Genes · doi:10.3390/genes8060148 · Cited by 427
Metadata
- Authors
- Liao, J., Karnik, R., Gu, H., Ziller, M. J., Clement, K., Tsankov, A. M., Akopian, V., Gifford, C. A., Donaghey, J., Galonska, C., Pop, R., Reyon, D., Tsai, S. Q., Mallard, W., Joung, J. K., Rinn, J. L., Gnirke, A., & Meissner, A.
- Venue
- Nature Genetics
- Published
- 2015-03-30
- Volume
- 47
- Issue
- 5
- Pages
- 469-478
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1977463456
- Cited by
- 476
- References
- 14
- FWCI
- 23.54
- Type
- journal article
- Language
- en
- Open access
- green
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