CpG methylation is maintained in human cancer cells lacking DNMT1

Ina Rhee, Kam Wing Jalr, Ray-Whay Yen, Christoph Lengauer, James G. Herman, Kenneth W Kinzler, Bert Vogelstein, Stephen B Baylin, Kornel Schuebel

Research output: Contribution to journalArticle

Abstract

Hypermethylation is associated with the silencing of tumour susceptibility genes in several forms of cancer; however, the mechanisms responsible for this aberrant methylation are poorly understood. The prototypic DNA methyltransferase, DNMT1, has been widely assumed to be responsible for most of the methylation of the human genome, including the abnormal methylation found in cancers. To test this hypothesis, we disrupted the DNMT1 gene through homologous recombination in human colorectal carcinoma cells. Here we show that cells lacking DNMT1 exhibited markedly decreased cellular DNA methyltransferase activity, but there was only a 20% decrease in overall genomic methylation. Although juxtacentromeric satellites became significantly demethylated, most of the loci that we analysed, including the tumour suppressor gene p16(INK4a), remained fully methylated and silenced. These results indicate that DNMT1 has an unsuspected degree of regional specificity in human cells and that methylating activities other than DNMT1 can maintain the methylation of most of the genome.

Original languageEnglish (US)
Pages (from-to)1003-1007
Number of pages5
JournalNature
Volume404
Issue number6781
DOIs
StatePublished - Apr 27 2000

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Methylation
Methyltransferases
Neoplasms
Homologous Recombination
DNA
Human Genome
Tumor Suppressor Genes
Genes
Colorectal Neoplasms
Genome

ASJC Scopus subject areas

  • General

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CpG methylation is maintained in human cancer cells lacking DNMT1. / Rhee, Ina; Jalr, Kam Wing; Yen, Ray-Whay; Lengauer, Christoph; Herman, James G.; Kinzler, Kenneth W; Vogelstein, Bert; Baylin, Stephen B; Schuebel, Kornel.

In: Nature, Vol. 404, No. 6781, 27.04.2000, p. 1003-1007.

Research output: Contribution to journalArticle

Rhee I, Jalr KW, Yen R-W, Lengauer C, Herman JG, Kinzler KW et al. CpG methylation is maintained in human cancer cells lacking DNMT1. Nature. 2000 Apr 27;404(6781):1003-1007. https://doi.org/10.1038/35010000
Rhee, Ina ; Jalr, Kam Wing ; Yen, Ray-Whay ; Lengauer, Christoph ; Herman, James G. ; Kinzler, Kenneth W ; Vogelstein, Bert ; Baylin, Stephen B ; Schuebel, Kornel. / CpG methylation is maintained in human cancer cells lacking DNMT1. In: Nature. 2000 ; Vol. 404, No. 6781. pp. 1003-1007.
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AU - Jalr, Kam Wing

AU - Yen, Ray-Whay

AU - Lengauer, Christoph

AU - Herman, James G.

AU - Kinzler, Kenneth W

AU - Vogelstein, Bert

AU - Baylin, Stephen B

AU - Schuebel, Kornel

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