Abstract
Little is known about the impact of space (geography/ancestry) and time (age of the individuals) on DNA methylation variability in humans. We investigated DNA methylation of the imprinted IGF2/H19 locus in: i) a cohort of individuals homogeneous for age and gender (males with restricted age range: 30-50 years) belonging to four Italian districts representative of the major genetic clines, informative for the geographical dimension; ii) a cohort of monozygotic (MZ) and dizygotic (DZ) twins of different ages (age-range: 22-97 years), informative for the temporal dimension. DNA methylation of the analyzed regions displayed high levels of inter-individual variability that could not be ascribed to any geographical cline. In MZ twins we identified two IGF2/H19 regions where the intra-couple variations significantly increased after the age of 60 years. The analysis of twins' individual life histories suggests that the within twin pairs difference is likely the result of the aging process itself, as sharing a common environment for long periods had no effect on DNA methylation divergence. On the whole, the data here reported suggest that: i) aging more than population genetics is responsible for the inter-individual variability in DNA methylation patterns in humans; ii) DNA methylation variability appears to be highly region-specific.
Highlights
DNA methylation is widespread across the genomes of different organisms and in mammals usually consists in the enzymatic addition of a methyl group to the carbon5 of cytosine ring of a CpG dinucleotide
IGF2AS and H19 DNA methylation values were comparable to those previously reported in literature [16, 17]
Our results indicate that the 4 analyzed regions in the IGF2/H19 locus show high inter-individual variability both in cohort 1 and in cohort 2
Summary
DNA methylation is widespread across the genomes of different organisms and in mammals usually consists in the enzymatic addition of a methyl group to the carbon of cytosine ring of a CpG dinucleotide. While the bulk of human genome is generally methylated, the promoters of around 40% of genes contain CpG-rich regions, termed CpG islands, whose methylation status is strictly regulated during development and cellular differentiation [1,2,3]. More recently it has been shown that tissue- and disease-specific differentially methylated regions (DMR) are more frequent in CpG island shores rather than in CpG islands [4, 5]. DNA methylation is generally considered a stable modification, it is well established that methylation profiles vary in pathological conditions, and it is accepted that external factors, such as diet, age, toxins and lifestyle, can induce quantitative hypoor hyper- DNA methylation [6,7,8,9,10,11,12,13]. Few studies have focused the effect of such factors on interwww.impactaging.com
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