Research Article: Space/Population and Time/Age in DNA methylation variability in humans: a study on IGF2/H19 locus in different Italian populations and in mono- and di-zygotic twins of different age

Date Published: July 31, 2012

Publisher: Impact Journals LLC

Author(s): Chiara Pirazzini, Cristina Giuliani, Maria Giulia Bacalini, Alessio Boattini, Miriam Capri, Elisa Fontanesi, Elena Marasco, Vilma Mantovani, Michela Pierini, Elisa Pini, Donata Luiselli, Claudio Franceschi, Paolo Garagnani.

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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.

Partial Text

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-5 of cytosine ring of a CpG dinucleotide. Through the recruitment of methyl-binding proteins, this modification induces an inactive chromatin structure that represses transcription. 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 [1-3]. Deregulation in methylation patterns can lead to disease onset. 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].

Our results indicate that the 4 analyzed regions in the IGF2/H19 locus show high inter-individual variability both in cohort 1 (spatial/population dimension) and in cohort 2 (temporal/aging dimension). IGF2AS and H19 have mean methylation values comparable to previous reports [16,17], indicating that methylation profiles are consistent among different populations and that the experimental technique used for methylation analysis is highly reproducible between independent laboratories. On the contrary, IGF2_island and IGF2_shore were analyzed for their methylation values here for the first time.

 

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