Why is DNA methylation of Igf2 CpG island shore affected during ageing?

post-genomic era attention has been focused on the characterization of the human DNA " methylome " at single nucleotide resolution. It is a particularly difficult goal to achieve as methylation profiling is different in tissues and cells of the same individual. 5-Methylcytosine is considered the " fifth base " of DNA as it introduces an epigenetic code on genome which is defined during development. Nutrition, environment and style of life have an impact on the " methylome " and the introduction of anomalous methyl groups in sequences that have to be maintained unmethylated and/or demethylation of chromatin regions which are usually methylated drive the biological events associated with pathologies. The same anomalies in methylation patterns occur with age so an in-depth knowledge of these changes will help us to individuate what leads to the passage from successful ageing to one in which there is the onset of disease [1]. Data from Franceschi's group are focused on ageing and the cohorts of individuals are selected in order to establish whether variability in DNA methylation patterns is to ascribe to age of individuals rather than to their geographical dimension. Notably, in this study monozygotic and dizygotic twins of ages ranging from 22 to 97 years are also enrolled. Four regions, located at the Igf2/H19 imprinted locus, were analyzed including the CpG island present in differentially methylated region 2 (DMR2) and the nearby 5' shore, two fragments never investigated up to now. Authors conclude that the shore is the one in which the scatter in methylation variability during ageing is more evident. Shore regions, which localize in proximity of CpG islands at 200-2000 kb away from them, are of particular interest as involved in gene expression regulation through the DMRs often located within them [2]. A long-range looping interaction is involved in the control of imprinting at maternally inherited allele at the Igf2/H19 gene locus. An interesting hypothesis for sus-Editorial Comment ceptibility to epimutation of this shore region in aged individuals is that its position inside the loop is topologically responsible for its availability to change the methylation profile. Although the higher order chromatin organization at Igf2/H19 locus is well assessed in mice, less information is available in humans. Anyway, the analysis of data about chromatin structure from the ENCODE consortium, accessible at the UCSC Genome Browser (http://genome.ucsc.edu/) [3, 4], indicates a distinctive chromatin feature of this shore region which corresponds to an …