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DNA Research Advance Access published online on October 26, 2006

DNA Research, doi:10.1093/dnares/dsl008
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© The Author 2006. Kazusa DNA Research Institute.
Received May 24, 2006
Revised August 22, 2006

Full Papers

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

Jieun Cheong 1, Yoichi Yamada 2, Riu Yamashita 3, Takuma Irie 4, Akinori Kanai 4, Hiroyuki Wakaguri 4, Kenta Nakai 5, Takashi Ito 6, Izumu Saito 1, Sumio Sugano 4, and Yutaka Suzuki 4 *

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

* To whom correspondence should be addressed.
Yutaka Suzuki, E-mail: ysuzuki{at}hgc.jp


   Abstract

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.

Keywords: DNA methylation status; CpG islands.
Communicated by Yoichi Taya
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