RT Journal
A1 Yagi, Shintaro
A1 Hirabayashi, Keiji
A1 Sato, Shinya
A1 Li, Wei
A1 Takahashi, Yoko
A1 Hirakawa, Tsutomu
A1 Wu, Guoying
A1 Hattori, Naoko
A1 Hattori, Naka
A1 Ohgane, Jun
A1 Tanaka, Satoshi
A1 Liu, X. Shirley
A1 Shiota, Kunio
T1 DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) in mouse promoter regions demonstrating tissue-specific gene expression
JF Genome Research 
JO Genome Research 
YR 2008 
FD December 01 
VO 18 
IS 12 
SP 1969 
OP 1978 
DO 10.1101/gr.074070.107 
UL http://genome.cshlp.org/content/18/12/1969.abstract 
AB 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 multilayered regulation of tissue-specific gene function could be elucidated by DNA methylation tissue profiling.