DNA unmethylome profiling via covalent capture of CpG sites. Homo sapiens

Cytosine 5-modification is a widespread epigenetic mark in eukaryote genomes including humans, but its large scale populational studies are hampered by substantial limitations of the existing analytical techniques. We have developed a new approach for mapping of the unmodified fraction of the genome, i.e. DNA unmethylome, which is based on covalent tagging of unmodified CpG sites with biotin. Sequence-specific tagging of DNA was achieved by using an engineered version of the SssI cytosine-5 methyltransferase and a synthetic analog of the S-adenosylmethionine cofactor carrying a transferable 6-aminohex-2-ynyl group. Analysis of the streptavidin-enriched human unmethylome on tiling DNA microarrays showed that the new approach (named mTAG-chip) offers nanogram sensitivity, a substantially higher precision in the low and medium CpG density regions and added versatility as compared with the existing epigenome profiling techniques. Overall design: AC103, AC13 and AC31 are DNA samples from three postmortem brains. Nr1 and Nr2 are two replicates of each sample. 5%, 20% and 70% are labeling efficiency. K means 0% labeling efficiency. We were testing which labeling efficiency was best by comparing to published seq data using correlation. **All of the data described in PMID 23877302 is included in Series GSE48994 and GSE49044.