Postnatal development- and age-related changes in DNA methylation patterns in the human genome

Multiple examples of epigenetic change, including alterations in DNA methylation, have been reported to occur during development and aging. However, much remains to be learned on regarding postnatal and age-associated epigenome dynamics, as few if any studies have compared human methylome patterns on a whole genome basis in cells from newborns and adults. The aim of this study was to reveal genomic regions with distinct structure and sequence characteristics which render them subject to dynamic postnatal developmental remodeling or age-related deregulation of epigenome structure. DNA samples derived from peripheral blood monocytes and in vitro differentiated dendritic cells were analyzed by Methylated DNA Immunoprecipitation (MeDIP) followed by Next Generation Sequencing (MeDIP-Seq). Differences in methylome data due to individual variation were minimized by pooling DNA samples for each age group and by requiring consistent changes in multiple data sets. Regions of methylation change that emerged from the analysis were high in GC-content and typically enriched for CpG clusters smaller than CpG islands. One group consisted of tandem or interspersed-tandem gene sequence repeats (PCDHG, FAM90A and HRNR), while a second group contained, or were adjacent to, genes with high homology to other gene family members elsewhere in the genome (ECEL1P2, FZD1, FZD7, and FGF17). We propose that sequences with these characteristics may provide a mechanistic basis for progressive methylation changes during postnatal development and for subsequent epigenetic deregulation with age.