DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) in mouse promoter regions demonstrating tissue-specific gene expression

Shintaro Yagi, Keiji Hirabayashi, Shinya Sato, Wei Li, Yoko Takahashi, Tsutomu Hirakawa, Guoying Wu, Naoko Hattori, Naka Hattori, Jun Ohgane, Satoshi Tanaka, X. Shirley Liu, Kunio Shiota*

*この研究の対応する著者

研究成果: Article査読

128 被引用数 (Scopus)

抄録

DNA methylation constitutes an important epigenetic regulation mechanism in many eukaryotes, although the extent of DNA methylation in the regulation of gene expression in the mammalian genome is poorly understood. We developed D-REAM, a genome-wide DNA methylation analysis method for tissue-dependent and differentially methylated region (T-DMR) profiling with restriction tag-mediated amplification in mouse tissues and cells. Using a mouse promoter tiling array covering a region from ?6 to 2.5 kb (∼30,000 transcription start sites), we found that over 3000 T-DMRs are hypomethylated in liver compared to cerebrum. The DNA methylation profile of liver was distinct from that of kidney and spleen. This hypomethylation profile marked genes that are specifically expressed in liver, including key transcription factors such as Hnf1a and Hnf4a. Genes with T-DMRs, especially those lacking CpG islands and those with HNF-1A binding motifis in their promoters, showed good correlation between their tissue-specific expression and liver hypomethylation status. T-DMRs located downstream from their transcription start sites also showed tissue-specific gene expression. These data indicate that multi-layered regulation of tissue-specific gene function could be elucidated by DNA methylation tissue profiling.

本文言語English
ページ(範囲)1969-1978
ページ数10
ジャーナルGenome Research
18
12
DOI
出版ステータスPublished - 2008 12
外部発表はい

ASJC Scopus subject areas

  • 遺伝学
  • 遺伝学(臨床)

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