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CpG methylation is maintained in human cancer cells lacking DNMT1

Author

Listed:
  • Ina Rhee

    (The Howard Hughes Medical Institute,
    The Johns Hopkins Oncology Center
    The Program in Human Genetics, Johns Hopkins University School of Medicine)

  • Kam-Wing Jair

    (The Johns Hopkins Oncology Center)

  • Ray-Whay Chiu Yen

    (The Johns Hopkins Oncology Center)

  • Christoph Lengauer

    (The Johns Hopkins Oncology Center)

  • James G. Herman

    (The Johns Hopkins Oncology Center)

  • Kenneth W. Kinzler

    (The Johns Hopkins Oncology Center
    The Program in Human Genetics, Johns Hopkins University School of Medicine)

  • Bert Vogelstein

    (The Howard Hughes Medical Institute,
    The Johns Hopkins Oncology Center
    The Program in Human Genetics, Johns Hopkins University School of Medicine)

  • Stephen B. Baylin

    (The Johns Hopkins Oncology Center
    The Program in Human Genetics, Johns Hopkins University School of Medicine)

  • Kornel E. Schuebel

    (The Johns Hopkins Oncology Center)

Abstract

Hypermethylation is associated with the silencing of tumour susceptibility genes in several forms of cancer1,2; however, the mechanisms responsible for this aberrant methylation are poorly understood3,4. 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 cancers5,6. 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 p16INK4a, 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.

Suggested Citation

  • Ina Rhee & Kam-Wing Jair & Ray-Whay Chiu Yen & Christoph Lengauer & James G. Herman & Kenneth W. Kinzler & Bert Vogelstein & Stephen B. Baylin & Kornel E. Schuebel, 2000. "CpG methylation is maintained in human cancer cells lacking DNMT1," Nature, Nature, vol. 404(6781), pages 1003-1007, April.
    • Handle: RePEc:nat:nature:v:404:y:2000:i:6781:d:10.1038_35010000
    DOI: 10.1038/35010000
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    Cited by:

    1. Bo Zhang & Wei Zhu & Ping Yang & Tao Liu & Mei Jiang & Zhi-Ni He & Shi-Xin Zhang & Wei-Qing Chen & Wen Chen, 2011. "Cigarette Smoking and p16INK4α Gene Promoter Hypermethylation in Non-Small Cell Lung Carcinoma Patients: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 6(12), pages 1-9, December.
    2. Gerardo Alfonso Perez & Javier Caballero Villarraso, 2021. "Alzheimer Identification through DNA Methylation and Artificial Intelligence Techniques," Mathematics, MDPI, vol. 9(19), pages 1-14, October.

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