Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Technical Report
  • Published:

Genome-wide profiling of promoter methylation in human

Oncogene volume 25, pages 3059–3064 (2006)Cite this article

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  • Abujiang P, Mori TJ, Takahashi T, Tanaka F, Kasyu I, Hitomi S et al. (1998). Oncogene 17: 3029–3033.

  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ . (1990). J Mol Biol 215: 403–410.

  • Baylin SB, Herman JG, Graff JR, Vertino PM, Issa J-P . (1997) In: Vande W and Klein G (eds). Advances in Cancer Research. Academic Press: San Diego. pp 141–196.

    Google Scholar 

  • Boyes J, Bird A . (1992). EMBO J 11: 327–333.

  • Hatada I, Kato A, Morita S, Obata Y, Nagaoka K, Sakurada A et al. (2002). J Hum Genet 47: 448–451.

  • Heisler LE, Torti D, Boutrous PC, Watson J, Chan C, Winegarden N et al. (2005). Nucleic Acids Res 33: 2952–2961.

  • Hughes TR, Mao M, Jones AR, Burchard J, Marton MJ, Shannon KW et al. (2001). Nat Biotechnol 19: 342–347.

  • Inohara N, Koseki T, Chen S, Wu X, Nunez G . (1998). EMBO J 17: 2526–2533.

  • Jager AC, Bisgaard ML, Myrhoj T, Bernstein I, Rehfeld JF, Nielsen FC . (1997). Am J Hum Genet 61: 129–138.

  • Lipkin SM, Wang V, Jacoby R, Banerjee-Basu S, Baxevanis AD, Ly nch HT et al. (2000). Nat Genet 24: 27–35.

  • Papadopoulos N, Nicolaides NC, Wei YF, Ruben SM, Carter KC, Rosen CA et al. (1994). Science 263: 1625–1629.

  • Rozen S, Skaletsky HJ . (2000) In: Krawetz S and Misener S (eds). Bioinformatics Methods and Protocols: Methods in Molecular Biology. Humana Press: Totowa. pp 365–386.

    Google Scholar 

  • Takai D, Jones PA . (2002). Proc Natl Acad Sci USA 99: 3740–3745.

  • Ushijima T . (2005). Nat Rev Cancer 5: 223–231.

  • Weber M, Davies JJ, Wittig D, Oakeley EJ, Haase M, Lam WL et al. (2005). Nat Genet 37: 853–862.

  • Yan PS, Chen CM, Shi H, Rahmatpanah F, Wei SH, Caldwell CW et al. (2001). Cancer Res 61: 8375–8380.

Download references

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.

Author information

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Fukasawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Morita
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T Yoshikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S Yamanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C Endo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A Sakurada
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. T Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A Horii
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. T Ushijima
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. H Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I Hatada.

Additional information

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

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

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

Keywords

This article is cited by

Search

Advanced search

Quick links