The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
DNMT1 but not its interaction with the replication machinery is required for maintenance of DNA methylation in human cells
Open accessAbstract
DNA methylation plays a central role in the epigenetic regulation of gene expression in vertebrates. Genetic and biochemical data indicated that DNA methyltransferase 1 (Dnmt1) is indispensable for the maintenance of DNA methylation patterns in mice, but targeting of the DNMT1 locus in human HCT116 tumor cells had only minor effects on genomic methylation and cell viability. In this study, we identified an alternative splicing in these cells that bypasses the disrupting selective marker and results in a catalytically active DNMT1 protein lacking the proliferating cell nuclear antigen–binding domain required for association with the replication machinery. Using a mechanism-based trapping assay, we show that this truncated DNMT1 protein displays only twofold reduced postreplicative DNA methylation maintenance activity in vivo. RNA interference–mediated knockdown of this truncated DNMT1 results in global genomic hypomethylation and cell death. These results indicate that DNMT1 is essential in mouse and human cells, but direct coupling of the replication of genetic and epigenetic information is not strictly required.
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Cites
DNA methylation patterns and epigenetic memory
Bird, A. (2002) · Genes & Development · doi:10.1101/gad.947102 · Cited by 7,124
Targeted mutation of the DNA methyltransferase gene results in embryonic lethality
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Induction of tumors in mice by genomic hypomethylation
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“lation, are runted, and develop aggressive T cell lymphomas (Gaudet et al., 2003).”
BackgroundInfluentialSelf-citationDe novo DNA cytosine methyltransferase activities in mouse embryonic stem cells
Lei, H., Oh, S. P., Okano, M., Jüttermann, R., Goss, K. A., Jaenisch, R., & Li, E. (1996) · Development · doi:10.1242/dev.122.10.3195 · Cited by 816
Cited by
UHRF1 Plays a Role in Maintaining DNA Methylation in Mammalian Cells
Bostick, M., Kim, J. K., Estève, P.-O., Clark, A., Pradhan, S., & Jacobsen, S. E. (2007) · Science · doi:10.1126/science.1147939 · Cited by 1,455
The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA
Sharif, J., Muto, M., Takebayashi, S.-I., Suetake, I., Iwamatsu, A., Endo, T. A., Shinga, J., Mizutani-Koseki, Y., Toyoda, T., Okamura, K., et al. (2007) · Nature · doi:10.1038/nature06397 · Cited by 1,304
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Interpreting the language of histone and DNA modifications
Rothbart, S. B., & Strahl, B. D. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.03.001 · Cited by 720
The social environment and the epigenome
Szyf, M., McGowan, P., & Meaney, M. J. (2008) · Environmental and Molecular Mutagenesis · doi:10.1002/em.20357 · Cited by 531
Metadata
- Authors
- Spada, F., Haemmer, A., Kuch, D., Rothbauer, U., Schermelleh, L., Kremmer, E., Carell, T., Längst, G., & Leonhardt, H.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2007-02-20
- Volume
- 176
- Issue
- 5
- Pages
- 565-571
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2141963489
- Cited by
- 192
- References
- 4
- FWCI
- 7.06
- Type
- journal article
- Language
- en
- Open access
- green
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- Spada, F., Haemmer, A., Kuch, D., Rothbauer, U., Schermelleh, L., Kremmer, E., Carell, T., Längst, G., & Leonhardt, H. (2007). DNMT1 but not its interaction with the replication machinery is required for maintenance of DNA methylation in human cells. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200610062
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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