Some people believe that the right sports car, dog, or teeth whitener will turn them into an irresistible magnet for the opposite sex. While impressive epigenetics knowledge may not help you attract Mr./Ms. Right, two recent papers strengthen the case that single-nucleotide variants can act as powerful magnets for DNA methylation.
In the first paper (PLoS Genetics, August 2011), researchers used reduced representation bisulfite sequencing (RRBS) to probe DNA methylation patterns in six members of a three-generation family. They then correlated the methylation status of CpG dinucleotides with the presence of nearby SNPs. Their findings:
- Homologous chromosomes frequently showed differential methylation, often in intergenic regions
- In general, SNPs appeared to influence methylation levels of homologous chromosomes more strongly than the parental origin of the chromosome (i.e., imprinting)
The researchers conclude that “genetics plays a prominent role in the establishment of DNA methylation patterns.” SNPs could create or abolish CpG sites or attract or repel the DNA methylation machinery, they say.
In the second paper (Cancer Cell, August 2011), a different group of researchers provides an example of why SNPs matter to DNA methylation. They studied three generations of a large family whose members have an increased risk of developing cancer at a young age. The team found that:
- Family members carried two SNPs (c.-27C > A and c.85G > T) in the promoter of MLH1, a DNA mismatch repair gene previously linked to cancer susceptibility
- Relatives with these SNPs had methylated MLH1, whereas those lacking the SNPs did not
- The altered MLH1 methylation was reset in spermatozoa but then reestablished in the soma of the next generation
- c.-27C > A alone decreased transcriptional activity of MLH1
“What we found was that a subtle change near the gene was acting like a magnet to attract methylation,” says study co-leader Megan Hitchins at the University of New South Wales, in Australia. “So it was not the methylation itself that was being passed from parent to child, but rather the DNA change, and this acted as a methyl magnet.”