Techniques for assessing genome-wide DNA methylation have been evolving rapidly over the past few years. The goal is to survey sequences throughout the genome, particularly those in “CpG islands” and promoters, for the presence of 5-methylcytosine (5mC) enrichment to identify differentially-methylated regions (DMRs) that might be linked with epigenetic regulation of adjacent genes. The first genome-wide methods were modifications of protocols using microarrays with probes designed to sample the genome at a reasonably high density. For example, the commonly-used Nimblegen arrays are designed to cover all known CpG-rich regions and transcription promoters by "tiling" 50 nucleotide (nt) probes with an average spacing of 50 base pairs (bp) of non-probed sequence separating each probed sequence. In some examples, sheared fragments of genomic DNA from the selected sample are immunoprecipitated with antibodies specific for 5mC and this methyl-enriched DNA is compared with unenriched DNA using contrasting probe dye colors. This is a cost-effective way to sample nearly half of all CpG islands and promoter regions on a microarray with the then-available probe densities. A similar approach uses Affymetrix promoter-focused microarrays. In this
