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DNA Research Advance Access originally published online on October 26, 2006
DNA Research 2006 13(4):155-167; doi:10.1093/dnares/dsl008
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© The Author 2006. Kazusa DNA Research Institute
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Diverse DNA Methylation Statuses at Alternative Promoters of Human Genes in Various Tissues

Jieun Cheong1,2, Yoichi Yamada3, Riu Yamashita4, Takuma Irie1, Akinori Kanai1, Hiroyuki Wakaguri1, Kenta Nakai1,4, Takashi Ito5, Izumu Saito1,2, Sumio Sugano1 and Yutaka Suzuki1,*

1 Department of Medical Genome Sciences, Graduate School of Frontier Sciences, the University of Tokyo 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan
2 Graduate School of Medicine, the University of Tokyo 7-3-1 Hongo, Bunkyoku, Tokyo 113-0033, Japan
3 Division of Electrical Engineering and Computer Science, Graduate School of Natural Science and Technology, Kanazawa University Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan
4 Human Genome Center, Institute of Medical Science, the University of Tokyo 4-6-1 Shirokanedai, Minatoku, 108-8639 Tokyo, Japan
5 Department of Computational Biology, Graduate School of Frontier Sciences, the University of Tokyo 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561, Japan

We characterized the DNA methylation status at 144 tissue-biased and 37 non-tissue-biased alternative promoters of 61 human genes in five normal tissues. Analysis of the collected data revealed that (i) DNA methylation status differed greatly among alternative promoters belonging to the same gene; (ii) DNA methylation status differed between tissues for the majority of the individual promoters, and (iii) 80–90% of CpG-island-containing promoters were not methylated on either allele throughout the five tissues examined. Furthermore, although the statistical significance was not as clear as for the above features, we also found that (iv) the DNA methylation patterns of tissue-biased promoters changed more drastically than those of non-tissue-biased promoters; (v) tissue-biased promoters tended to be less methylated than their respective alternative promoters in the tissues where they were preferentially expressed, and (vi) the ‘null’ methylation pattern of a given promoter was enriched in the tissues where the transcription was most active. These findings together indicate that there are dynamic physiological changes of DNA methylation. DNA methylation appears to play a significant role in differential usage of alternative promoters and may be related to functional diversification between CpG-island-containing promoters and CpG-island-less promoters.

Key words: DNA methylation status; CpG islands

*To whom correspondence should be addressed. Tel. +81-4-7136-3607, Fax. +81-4-7136-3607, E-mail: ysuzuki{at}hgc.jp

Communicated by Yoichi Taya


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