It seems like all news lately is focused on the terrors of the world and transgenerational epigenetic inheritance has been no exception, usually with a strong focus on how an exposure or trauma finds a way to haunt generations. But now now an optimistic team from UCLA have shown that a lot can be learned from examining how DNA methylation is transmitted across generations in a ‘wild-type’ fashion.
In order to determine just how DNA methylation differs across one generation, the team examined the classical lab mouse strains (C57BL/6J and DBA/2J) and their F1 crosses using RRBS bisulfite sequencing. Here’s what they found:
- There are a lot of reproducible methylation differences between the CpGs of the two strains.
- These differences are also heritable between the parents and their F1 cross progeny.
- There are about 400 genes with sex differences in methylation and 11% of them show differential expression across sexes.
As an added bonus, the team unveiled a fancy technique to detect allelically methylated regions (AMRs). The benefit of this one is that it is not limited to the use of SNPs to distinguish parent of origin. This approach identified 112 novel imprinted genes and miRNAs and the group went on to validate genomic imprinting at the RNA level in 10 of the genes. The authors conclude that the majority of DNA methylation differences across strains are related to genetic differences, with only a small amount be due to gender, genomic imprinting, or other stochastic transgenerational effects. However, they also point that these differences can be determining factor for heritability given the observed functional consequences and should be considered in all association studies for molecular and clinical traits.
Learn all about wild-type epigenetic inheritance in Genome Biology, June 2014