The best-studied kind of epigenetic modification of DNA in humans is methylation of cytosine at position C5 in CpG dinucleotides.16 More than 28 million CpG sites are distributed across the human genome,17 and 70–80% of them can be methylated.18 It is estimated that there are about 45,000 CpG islands (or clusters of CpG dinucleotides in GC-rich regions) per haploid human genome.19 CpG islands typically occur at or near the transcription start site (or the promoter region) of genes and are often hypomethylated.20,21 In the cell, methylation of CpG sites (especially those in CpG islands located in promoter regions) may influence gene transcription via at least two mechanisms: (i) DNA methylation inhibits the binding of transcription factors (TFs) to the promoter region, and thus, directly interferes with gene transcription22–24; and (ii) DNA methylation attracts methyl CpG binding proteins (such as MeCP2) to the promoter region, and subsequently, methyl CpG binding proteins recruit a variety of histone deacetylase (HDAC) complexes and chromatin remodeling factors, leading to chromatin compaction and transcriptional repression.25 DNA methylation at CpG dinucleotides plays a central role in many
