Impact of the Genome on the Epigenome Is Manifested in DNA Methylation Patterns of Imprinted Regions in Monozygotic and Dizygotic Twins

University of Illinois at Chicago, United States of America
PLoS ONE (Impact Factor: 3.23). 10/2011; 6(10):e25590. DOI: 10.1371/journal.pone.0025590
Source: PubMed


One of the best studied read-outs of epigenetic change is the differential expression of imprinted genes, controlled by differential methylation of imprinted control regions (ICRs). To address the impact of genotype on the epigenome, we performed a detailed study in 128 pairs of monozygotic (MZ) and 128 pairs of dizygotic (DZ) twins, interrogating the DNA methylation status of the ICRs of IGF2, H19, KCNQ1, GNAS and the non-imprinted gene RUNX1. While we found a similar overall pattern of methylation between MZ and DZ twins, we also observed a high degree of variability in individual CpG methylation levels, notably at the H19/IGF2 loci. A degree of methylation plasticity independent of the genome sequence was observed, with both local and regional CpG methylation changes, discordant between MZ and DZ individual pairs. However, concordant gains or losses of methylation, within individual twin pairs were more common in MZ than DZ twin pairs, indicating that de novo and/or maintenance methylation is influenced by the underlying DNA sequence. Specifically, for the first time we showed that the rs10732516 [A] polymorphism, located in a critical CTCF binding site in the H19 ICR locus, is strongly associated with increased hypermethylation of specific CpG sites in the maternal H19 allele. Together, our results highlight the impact of the genome on the epigenome and demonstrate that while DNA methylation states are tightly maintained between genetically identical and related individuals, there remains considerable epigenetic variation that may contribute to disease susceptibility.

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Available from: Marcel Coolen
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    • "transmitted via the male germ line during more than three generations . Nonetheless , some epigenetic mechanisms might be controlled by heritable genetic effects . There are genotypes that are more susceptible to methylation than others ( Coolen et al . , 2011 ) . Such as genotypes with a larger proportion of cytosines in the CpG islands that are more susceptible to methylation . Further , DNA codes for histone and DNA - folding proteins , which may also have epigenetic effects . These sorts of elements with potential epigenetic effects are heritable in an additive manner . The challenge here"
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    • "n‐modifiable nucleotide , or indirect by altering transcription factor binding , which in turn independently affects gene expression and DNA methylation levels ( Gutierrez‐ Arcelus et al . , 2013 ) . Polymorphisms may also affect imprinting locus control regions and thus have an influence on epigenetic changes associated with parental imprinting ( Coolen et al . , 2011 ) . This concept of allele‐specific methylation is growing in importance with the recognition that this phenomenon may extend well beyond classical imprinted genes ."
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