Small DMRs are differentially DNA-methylated genomic regions with sizes typically < 5k (smaller than the 5 Kb ~ 10 Mbp hypomethylated blocks). More than 10,000 cancer-specific DMRs have been identified, which could undergo either hypomethylation(~4,000) or hypermethylation (~5,800) in cancer . Hypermethylated DMRs are mostly located within the CpG islands, whereas hypomethylated DMRs are in the CpG island shores within 2 kb of the CpG island boundaries. In cancer, small DMRs are involved in the loss of stability of DNA methylation, which can be classified in three types: (1) Shifting of methylation boundaries, either out of the CpG island leading to hypomethylation (Fig. 1a) or into the CpG island causing hypermethylation (Fig.1b); (2) Loss of normal methylation boundaries forming hypermethylated islands in cancer (Fig. 1c); and (3) Novel hypomethylation that arose de novo in highly methylated regions (Fig.1d). DMRs not following these patterns are currently not classified. The strongest relationship between gene expression and methylation was observed for hypomethylated shores is due to methylation boundary shifts.
Arraystar 4 X 180K DMR Microarray is specifically designed for the study of the DMRs in cancer. The array covers 12113 small DMRs that are differentially methylated in cancers, tissue types and cell differentiation, as well as 11380 CpG islands and CpG island shores nearby these small DMRs. The microarray not only detects cancer-specific methylation status changes, but also how the CpG island methylation boundaries shift and epigenetic domains lose stability, thus providing comprehensive view and direct analysis of cancer methylomes.
Figure 1. Classification of DMRs (shaded pink) in cancer. (a) a methylation boundary shift outward, (b) a methylation boundary shift inward, (c) a loss of methylation boundary, and (d) a novel hypomethylation DMR. Grey bars indicate the location of hypomethylation blocks, CpG islands, and gene exons. Tick marks along the bottom axis indicate the location of CpG sites .
1. Hansen, K. D., et al. (2011) Nat Genet 43 (8): 768-75.
2. Timp, W., et al. (2014) Genome Med 6 (8): 61.
• Covers more than 12,000 small differentially expressed regions that undergo either hyper- or hypo- methylation in cancers.
• More than 11,000 CpG islands and shores nearby these DMRs.
• Detects not only methylation status changes, but also the boundary shifts of the regions that are strongly correlated to gene expression changes.
• Dual color channels for MeDIP and input DNA, achieving excellent sensitivity and specificity.