Cited by 6,143Epigenetics and DNA MethylationGenetic Syndromes and ImprintingGenomics and Chromatin Dynamics

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DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development

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Okano, Masaki, Bell, Daphne W, Haber, Daniel A, Li, En·1999·Cell

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Abstract

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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Authors: Okano, M., Bell, D. W., Haber, D. A., & Li, E.
Affiliations: Harvard University (US)
Corresponding author: Li, En
ORCID: Bell, Daphne W
Haber, Daniel A
Li, En
Venue: Cell
Publisher: Elsevier BV
Published: 1999-10
Volume: 99
Issue: 3
Pages: 247-257
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/s0092-8674(00)81656-6
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 5038 d)
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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DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development

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