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

Abstract

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.

Diabetes Induces Aberrant DNA Methylation in the Proximal Tubules of the Kidney

“…We screened for DMRs by comparing the DNA methylation profile of the PT cells with those of the whole kidney, liver, and cerebrum in a genome-wide manner (Supplemental Figure 1). 10,11 Ontology analysis of genes neighboring the DMRs revealed that the genes expressed in the kidney were significantly enriched in the genes associated with the hypomethylated DMRs in the PT cells compared with other tissues (Supplemental Tables 1 and 2). We found the enrichment of genes related to mitochondrial function and the brush border, such as Sglt2 (Slc5a2) and Glut5 (Slc2a5), in the genes with PT-DMRs (Supplemental Tables 3 and 4).…”

“…This observation is concordant with previous reports indicating a generally, but not exclusively, negative correlation between DNA methylation and expression. 10,25 Because we investigated DMRs in the promoter regions, the correlation of the expression and methylation levels of the DMRs located outside the promoter under diabetic conditions remains to be clarified.…”

“…Such DMRs underlie tissue-dependent gene expressions and are considered to contain information about the fundamental functions of each organ. 9,10 In previous studies, we identified DMRs by comparing the DNA methylation status in different organs, including the liver, cerebrum, and kidney. 10,11 The DMRs observed in the kidney include those localized in kidney-specific transporters, which are hypomethylated in the kidney compared with other organs.…”

Oocyte-specific linker histone H1foo is an epigenomic modulator that decondenses chromatin and impairs pluripotency

“…Genomic DNA was extracted from ES cells as described previously. 31 Genomic DNA was digested with HindIII (Takara), and 5 μg of digested DNA was denatured with 0.3 M NaOH. Sodium metabisulfite (pH 5.0) and hydroquinone were added at final concentrations of 2.0 M and 0.5 mM, respectively.…”

Cell-Specific Polymorphism and Hormonal Regulation of DNA Methylation in Scavenger Receptor Class B, Type I

“…Clusters of CpGs, called CpG islands (CGIs), are often found in association with genes, most often in the promoters and first exons but also in regions more toward the 3¢ end ( Jones and Takai, 2001). Genome-scale DNA methylation analyses show that tissue-specific differentially methylated regions (tDMRs) are frequently in mammalian genomes and related to tissue-specific gene expression (Song et al, 2005;Rakyan et al, 2008;Yagi et al, 2008;Song et al, 2009).…”