More speculation about epigenetics and ways that epigenetic mechanisms of gene regulation could contribute to differences between individuals. Many cases, both in plants and animals, have to do with transposable elements, which makes a lot of sense since DNA methylation is involved in silencing the expression of transposable elements. Think about genetical genomics studies such as Gibbs & al (2010), where gene expression and DNA methylation is mapped to genomic regions. First, when expression QTL and methylation QTL coincide, it might be a good idea to start looking for transposable element insertions. Finding them are not as easy as finding SNPs, but hopefully, there will be SNPs tagging the actual variant and DNA methylation will spread outside of the inserted element to CpGs that are being typed. The element itself could of course work as a promoter, but it could also spread methylation into regulatory sequences of the gene, suppressing expression, or increase expression by changing the effect of an insulator.
Second, apparently the DNA methylation of transposable elements can sometimes be variable. This is the case with axin fused, Cabp-IAP and the agouti epialleles (Druker & al 2004; Vasicek & al 1997; Morgan & al 1999); among mice that carry the insertion there is DNA methylation variation causing phenotypic differences. This means that in populations where the insertion segregates, there should be a DNA methylation by gene interaction in the effect on the phenotype. I think that is fun, and I’d like to see someone find that in a mapping study. It might make things more difficult, though. The methylation–gene expression association might be hard to detect because it only exists in one of the alleles.
Third, maybe that is actually how a DNA methylation variant might escape reprogramming. Since some transposable elements are among the sequences that are not demethylated after fertilisation, and if that effect also applies to the newly inserted copy of the transposable element, our hypothetical regulatory methylation difference might be preserved through meiosis that way.
Gibbs, J. R., van der Brug, M. P., Hernandez, D. G., Traynor, B. J., Nalls, M. A., Lai, S. L., … & Singleton, A. B. (2010). Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain. PLoS genetics, 6(5), e1000952.
Morgan, H. D., Sutherland, H. G., Martin, D. I., & Whitelaw, E. (1999). Epigenetic inheritance at the agouti locus in the mouse. Nature genetics, 23(3), 314-318.
Vasicek, T. J., Zeng, L. I., Guan, X. J., Zhang, T., Costantini, F., & Tilghman, S. M. (1997). Two dominant mutations in the mouse fused gene are the result of transposon insertions. Genetics, 147(2), 777-786.
Druker, R., Bruxner, T. J., Lehrbach, N. J., & Whitelaw, E. (2004). Complex patterns of transcription at the insertion site of a retrotransposon in the mouse. Nucleic acids research, 32(19), 5800-5808.