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The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

DNMT1 and DNMT3b cooperate to silence genes in human cancer cells

Rhee, Ina, Bachman, Kurtis E., Park, Ben Ho, Jair, Kam-Wing, Yen, Ray-Whay Chiu, Schuebel, Kornel E., Cui, Hengmi, Feinberg, Andrew P., Lengauer, Christoph, Kinzler, Kenneth W., Baylin, Stephen B., Vogelstein, Bert·2002·Nature
DOI 10.1038/416552a
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Abstract

Inactivation of tumour suppressor genes is central to the development of all common forms of human cancer. This inactivation often results from epigenetic silencing associated with hypermethylation rather than intragenic mutations. In human cells, the mechanisms underlying locus-specific or global methylation patterns remain unclear. The prototypic DNA methyltransferase, Dnmt1, accounts for most methylation in mouse cells, but human cancer cells lacking DNMT1 retain significant genomic methylation and associated gene silencing. We disrupted the human DNMT3b gene in a colorectal cancer cell line. This deletion reduced global DNA methylation by less than 3%. Surprisingly, however, genetic disruption of both DNMT1 and DNMT3b nearly eliminated methyltransferase activity, and reduced genomic DNA methylation by greater than 95%. These marked changes resulted in demethylation of repeated sequences, loss of insulin-like growth factor II (IGF2) imprinting, abrogation of silencing of the tumour suppressor gene p16INK4a, and growth suppression. Here we demonstrate that two enzymes cooperatively maintain DNA methylation and gene silencing in human cancer cells, and provide compelling evidence that such methylation is essential for optimal neoplastic proliferation.

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Crossref · 10.1038/416552a

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3 of 3 references verified0 citation errors · 0 not checkable

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  • Transcriptomic analysis of brains of adult Tert+/+ and G1 Tert−/− mice showed significant and specific reduction in expression of Dnmt3b.

    “Transcriptomic analysis of the brains of adult Tert+/+ and first generation (G1) Tert−/− mice (with intact telomeres)16 showed significant and specific reduction in the expression of Dnmt3b (Figures S4E and S4F), a DNA methyltransferase responsible for the hypermethylation of p16Ink4a promoter.26”

    From TERT activation targets DNA methylation and multiple aging hallmarks (2024) · cites this paper as [26]

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Research works printed but not linked: 27

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Metadata

Authors
Rhee, I., Bachman, K. E., Park, B. H., Jair, K.-W., Yen, R.-W. C., Schuebel, K. E., Cui, H., Feinberg, A. P., Lengauer, C., Kinzler, K. W., Baylin, S. B., & Vogelstein, B.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2002-04
Volume
416
Issue
6880
Pages
552-556
ISSN
  • 0028-0836
  • 1476-4687
DOI
10.1038/416552a
Cited by
1,039
References
3
Language
en
Licence
www.springer.com/tdm (tdm)

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