The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development
Open accessAbstract
The establishment of DNA methylation patterns requires de novo methylation that occurs predominantly during early development and gametogenesis in mice. Here we demonstrate that two recently identified DNA methyltransferases, Dnmt3a and Dnmt3b, are essential for de novo methylation and for mouse development. Inactivation of both genes by gene targeting blocks de novo methylation in ES cells and early embryos, but it has no effect on maintenance of imprinted methylation patterns. Dnmt3a and Dnmt3b also exhibit nonoverlapping functions in development, with Dnmt3b specifically required for methylation of centromeric minor satellite repeats. Mutations of human DNMT3B are found in ICF syndrome, a developmental defect characterized by hypomethylation of pericentromeric repeats. Our results indicate that both Dnmt3a and Dnmt3b function as de novo methyltransferases that play important roles in normal development and disease.
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In the citing paper
“Approximately 50% of all genetic variants in CH occur in the gene DNMT3A (6), which encodes a de novo DNA methyltransferase enzyme responsible for establishing new DNA methylation patterns during development and stem cell fate decisions (7,8).”
From Txnip Enhances Fitness of Dnmt3a -Mutant Hematopoietic Stem Cells via p21 (2022) · cites this paper as [7]
In the citing paper
“Global deletion of mouse Dnmt1, Dnmt3b, or both Dnmt3a + Dnmt3b results in midgestation lethality [gestational day (GD) 9.5–11.5], while deletion of only Dnmt3a produces severe growth retardation and lethality by 4 weeks of age [ 70–72 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [72]
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Cites
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Self-citationCancer-epigenetics comes of age
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DNA methylation patterns and epigenetic memory
Bird, A. (2002) · Genes & Development · doi:10.1101/gad.947102 · Cited by 7,124
Jaenisch, R., & Bird, A. (2003) · Nature Genetics · doi:10.1038/ng1089 · Cited by 6,325
Functions of DNA methylation: islands, start sites, gene bodies and beyond
Jones, P. A. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3230 · Cited by 6,061
DNA methylation and its basic function
Moore, L. D., Le, T., & Fan, G. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.112 · Cited by 4,906
Human DNA methylomes at base resolution show widespread epigenomic differences
Lister, R., Pelizzola, M., Dowen, R. H., Hawkins, R. D., Hon, G., Tonti-Filippini, J., Nery, J. R., Lee, L., Ye, Z., Ngo, Q.-M., et al. (2009) · Nature · doi:10.1038/nature08514 · Cited by 4,673
Metadata
- Authors
- Okano, M., Bell, D. W., Haber, D. A., & Li, E.
- Affiliations
- Harvard University (US)
- Corresponding author
- Li, En
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1999-10
- Volume
- 99
- Issue
- 3
- Pages
- 247-257
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2060446375
- Cited by
- 6,143
- References
- 45
- Citations by year
- 2026: 157 · 2025: 206 · 2024: 230 · 2023: 260 · 2022: 248 · 2021: 279 · 2020: 301 · 2019: 295 · 2018: 315 · 2017: 315 · 2016: 340 · 2015: 341 · 2014: 331 · 2013: 315 · 2012: 289
- FWCI
- 33.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2r01gm052106-06)
- National Cancer Institute (R01CA082389, CA 82389)
- National Institute of General Medical Sciences (GM52106)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- DNMT3A, DNMT3B, DNA methyltransferases, de novo methylation, mouse development, embryonic stem cells, centromeric satellite repeats, ICF syndrome, gene targeting
- MeSH terms
- DNA Methyltransferase 3A, DNA Methyltransferase 3B, Animals, Blastocyst, Centromere, Crosses, Genetic, DNA (Cytosine-5-)-Methyltransferases, Homozygote, Humans, Immunologic Deficiency Syndromes, Male, Mammals, Mice, Inbred C57BL, Repetitive Sequences, Nucleic Acid, Stem Cells, Mice, Knockout, DNA Methylation, Mice
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