Overview of DNA Methylation (DNAm)
About 70% of CpG sites in the human genome are
methylated27. CpGs are
concentrated in CpG islands (CGIs) – regions at least 200 base pairs
(bp) in length – where C-G dinucleotides make up more than 50% of the
sequence1,28.
CGIs house the promoter regions of ~ 70% of human
genes29,28.
The effect of DNAm on gene expression is influenced by CpG density in
these promoter
regions30.
Different technologies have been developed for assessing DNAm, but
arrays and sequencing protocols form the basis of the literature. Both
rely on the bisulfite conversion of DNA. Arrays compare signal
intensities between methylated and unmethylated probes at specific sites
while in sequencing, the proportion of methylated Cytosines is
calculated. Three arrays have been most commonly used to study DNAm in
humans: the legacy IlluminaHumanMethylation27
BeadChip31 , the
Illumina HumanMethylation450
BeadChip32 and finally
the Illumina MethylationEPIC BeadChip
array33. Each arrays
features progressive expansion of CpG coverage and increased
representation of different regions of the genome. The EPIC array covers
~30x more CpGs compared to the Illumina 27K array and
puts greater focus on CpGs outside of CGIs as these regions are
important for gene
regulation33.