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A Novel Dnmt3a Isoform Produced from an Alternative Promoter Localizes to Euchromatin and Its Expression Correlates with Activede Novo Methylation
Open accessAbstract
Previous studies have shown that the Dnmt3b gene encodes multiple variants via alternative splicing. However, only one form of Dnmt3a has been identified to date. We report here the discovery of a small form of Dnmt3a, denoted Dnmt3a2, from both human and mouse. The transcript encoding Dnmt3a2 is initiated from a downstream intronic promoter. As a result, the Dnmt3a2 protein lacks the N-terminal 223 (human) or 219 (mouse) amino acid residues of the full-length Dnmt3a. Recombinant Dnmt3a2 protein displayed similar cytosine methyltransferase activity as Dnmt3a in vitro. However, Dnmt3a and Dnmt3a2 exhibited strikingly different subcellular localization patterns. Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. Dnmt3a2 is the predominant form in embryonic stem cells and embryonal carcinoma cells and can also be detected from testis, ovary, thymus, and spleen, whereas Dnmt3a is expressed at low levels ubiquitously. Comparison of human embryonal carcinoma cell lines with breast/ovarian cancer cell lines indicates that DNMT3A2 expression correlates with high de novo methylation activity. These findings suggest that Dnmt3a and Dnmt3a2 may have distinct DNA targets and different functions in development.
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Cites
DNA methylation patterns and epigenetic memory
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Self-citationTargeted mutation of the DNA methyltransferase gene results in embryonic lethality
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Self-citationEpigenetic Reprogramming in Mammalian Development
Reik, W., Dean, W., & Walter, J. (2001) · Science · doi:10.1126/science.1063443 · Cited by 3,078
De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells
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Cited by
Chen, T., Ueda, Y., Dodge, J. E., Wang, Z., & Li, E. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.16.5594-5605.2003 · Cited by 751
Self-citationXie, W., Barr, C. L., Kim, A., Yue, F., Lee, A. Y., Eubanks, J., Dempster, E. L., & Ren, B. (2012) · Cell · doi:10.1016/j.cell.2011.12.035 · Cited by 543
The functional consequences of alternative promoter use in mammalian genomes
Davuluri, R. V., Suzuki, Y., Sugano, S., Plass, C., & Huang, T. H.-M. (2008) · Trends in Genetics · doi:10.1016/j.tig.2008.01.008 · Cited by 408
Nuclear calcium signalling in the regulation of brain function
Bading, H. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3531 · Cited by 373
Structural insight into autoinhibition and histone H3-induced activation of DNMT3A
Guo, X., Wang, L., Li, J., Ding, Z., Xiao, J., Yin, X., He, S., Shi, P., Dong, L., Li, G., et al. (2015) · Nature · doi:10.1038/nature13899 · Cited by 361
Metadata
- Authors
- Chen, T., Ueda, Y., Xie, S., & Li, E.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-10
- Volume
- 277
- Issue
- 41
- Pages
- 38746-38754
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2057089696
- Cited by
- 368
- References
- 5
- FWCI
- 5.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Chen, T., Ueda, Y., Xie, S., & Li, E. (2002). A Novel Dnmt3a Isoform Produced from an Alternative Promoter Localizes to Euchromatin and Its Expression Correlates with Activede Novo Methylation. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m205312200
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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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