methylatedDNA_peripheralBlood

The goal of the experiment – genome-wide profiling of DNA methylation reveals a class of normally methylated CpG island promoters Keywords: DNA methylation, Methylated CpG island amplification coupled with promoter arrays, normal tissue DNA methylation was initially suggested to control tissue-specific gene expression in mammalian cells, but CpG islands (CGIs) were found to be generally free of methylation regardless of the expression status of the associated genes. Here, we have discovered an exceptional subset of autosomal genes associated with dense promoter CGIs (4.1% of all CGIs analyzed) that is methylated in normal tissues. We observed tissue-specific gene silencing for this class of genes, and provided evidence for a direct role of methylation in maintaining the silencing state via pharmacologic or genetic reduction in DNA methyltransferase activity. By comparing DNA sequences flanking the center of CGIs, we have identified five sequence motifs significantly enriched in genes with methylated CGIs, suggesting the influence of cis regulatory elements on the establishment and/or stability of DNA methylation. Together, these results provide important new insights into the role of CGI methylation in normal development and differentiation.