DNA methylation and histone modification

Monozygotic twins are identical at the DNA sequence level but studies have found some phenotypic differences of DNA methylation and histone modification profiles that may be the results of different exposures to environmental stressors. This may affect their susceptibility to different diseases such as cancer or autoimmune disorders (Kaminsky et al., 2009; Fraga et al., 2005; Javierre et al., 2010).

There is a prevalent epigenetic drift in monozygotic twins as they advance in age (Fraga et al., 2005). Fraga et al. (2005) investigated both global and locus-specific differences in DNA methylation and histone acetylation in identical twins of various ages. Their results revealed that young identical twin pairs are essentially identical in their epigenetic markings while older identical twin pairs demonstrate significant variations in epigenetic differences in DNA methylation and histone modification. These differential markers between twins are distributed throughout their genomes, affecting repeat DNA sequences and single-copy genes, and have an impact on gene expression.

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Interestingly, variations in gene expression in older twin pairs were four times greater than those observed in young twin pairs. They also found that that these epigenetic modifications were more distinctive in older MZ twins with different lifestyles and who had spent less of their lives together; this emphasized the significance of the role of environmental factors in translating a common genotype into a different phenotype.

In a subsequent study, Martin (2005) reported that epigenetic shifts in the aging identical twins could have arisen from endogenous stochastic mechanisms independent of environmental perturbations or could have resulted from such environmental perturbations. These results constitute the most detailed results of age-associated epigenetic alterations in MZ twins of human subjects.

In the same breath, Talens et al. (2012) conducted a study to investigate the occurrence of epigenetic changes over the adult lifespan in monozygotic twin pairs (N=230, 18-89 years). They examined the global DNA methylation differences and found that there was more variation within old MZ-pairs as compared to young pairs. Furthermore, elderly twins revealed a similar pattern of variations in DNA methylation after a 10 year follow-up.

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