Schema of commonly used approaches to assess global DNA methylation changes. The closed blue circles represent hypermethylated CpG dinucleotides in the promoter region of a given gene and the open circles represent unmethylated CpG dinucleotides for the same gene. The green circles represent methyl-binding proteins that bind specifically to methylated DNA sequences. In bisulfite conversion approaches, the DNA is chemically modified, which allows for generation of distinct sequences based on the original DNA methylation status of cytosines. In immunoprecipitation approaches, the DNA is immunoprecipitated with an antibody (shown in red) specific to methyl-binding proteins or 5-methyl-cytosines to enrich for segments with DNA methylation. In restriction enzyme approaches such as HELP used by Figueroa et al,⁵  the DNA is digested with enzymes that are either insensitive (cut methylated sequences) or sensitive (do not cut methylated sequences) to DNA methylation. In each assay, the DNA is labeled and amplified prior to hybridization to microarrays. Professional illustration by Kenneth X. Probst.