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Genome-wide profiling of promoter methylation in human

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Abstract

DNA methylation in the promoter region of a gene is associated with a loss of that gene's expression and plays an important role in gene silencing. The inactivation of tumor-suppressor genes by aberrant methylation in the promoter region is well recognized in carcinogenesis. However, there has been little study in this area when it comes to genome-wide profiling of the promoter methylation. Here, we developed a genome-wide profiling method called Microarray-based Integrated Analysis of Methylation by Isoschizomers to analyse the DNA methylation of promoter regions of 8091 human genes. With this method, resistance to both the methylation-sensitive restriction enzyme HpaII and the methylation-insensitive isoschizomer MspI was compared between samples by using a microarray with promoter regions of the 8091 genes. The reliability of the difference in HpaII resistance was judged using the difference in MspI resistance. We demonstrated the utility of this method by finding epigenetic mutations in cancer. Aberrant hypermethylation is known to inactivate tumour suppressor genes. Using this method, we found that frequency of the aberrant promoter hypermethylation in cancer is higher than previously hypothesized. Aberrant hypomethylation is known to induce activation of oncogenes in cancer. Genome-wide analysis of hypomethylated promoter sequences in cancer demonstrated low CG/GC ratio of these sequences, suggesting that CpG-poor genes are sensitive to demethylation activity in cancer.

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Acknowledgements

This work was supported in part by grants from the Japanese Science and Technology Agency (IH), the Ministry of Education, Culture, Sports, Science and Technology of Japan (IH), and the Ministry of Health, Labour and Welfare of Japan (IH). We thank the Cancer Cell Repository (Institute of Development, Aging and Cancer, Tohoku University) for providing cancer cell lines and Miss Asano for technical assistance.

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Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Laboratory of Genome Science, Biosignal Genome Resource Center, Gunma University, Maebashi, Japan

    I Hatada, M Fukasawa, M Kimura & S Morita

  2. PRESTO, Japan Science and Technology Corporation (JST), Kawaguchi, Japan

    I Hatada, M Fukasawa, M Kimura & S Morita

  3. Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Japan

    K Yamada & T Yoshikawa

  4. Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan

    S Yamanaka, C Endo, A Sakurada, M Sato & T Kondo

  5. Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Japan

    S Yamanaka & A Horii

  6. Carcinogenesis Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan

    T Ushijima

  7. Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics, Research Organization of Information and Systems, Mishima, Japan

    H Sasaki

  8. Department of Genetics, School of Life Science, Graduate University for Advanced Studies, Mishima, Japan

    H Sasaki

Authors
  1. I Hatada
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  2. M Fukasawa
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  3. M Kimura
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  4. S Morita
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  5. K Yamada
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  6. T Yoshikawa
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  7. S Yamanaka
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  8. C Endo
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  9. A Sakurada
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  10. M Sato
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  11. T Kondo
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  12. A Horii
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  13. T Ushijima
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  14. H Sasaki
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Corresponding author

Correspondence to I Hatada.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc)

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Hatada, I., Fukasawa, M., Kimura, M. et al. Genome-wide profiling of promoter methylation in human. Oncogene 25, 3059–3064 (2006). https://doi.org/10.1038/sj.onc.1209331

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  • DOI: https://doi.org/10.1038/sj.onc.1209331

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