Finding informative epigenetic targets in the genome is no easy task; however, cleverly composed studies previously reported on the discovery of correlated regions of systemic interindividual variation (or CoRSIVs) in humans – DNA methylation patterns that vary between individuals but remain consistent across tissues. Now, this talented team sets its sights on understanding this level of epigenetic variation in cattle to improve livestock farming output. Have they hit a DNA methylation bullseye?
A targeted team guided by Yi Athena Ren (Cornell University) and Robert A. Waterland (Baylor College of Medicine) took the bull by the horns and aimed to identify cow CoRSIVs by reanalyzing DNA methylation data from an already reported whole genome bisulfite sequencing-based study in tissues from three embryonic germ layers from two Holstein Friesian cows (milking them for all their worth, even though only one cow was lactating!). Their on-point new research suggests that CoRSIVs may exist in all mammals and indicates that understanding this epigenetic level of control may enhance livestock farming by optimizing agriculturally essential traits. They really have hit the DNA methylation bullseye!
Let’s hear from Chang and colleagues on how bullseying this level of epigenetic control may improve livestock farming:
- A focus on genomic blocks with ≥ 5 CpGs and a systemic interindividual variation index of at least 20 identifies 217 cattle CoRSIVs, which share significant characteristics with the human variety
- Similar to humans, cattle CoRSIVs strongly associate with genetic variation
- While not powered to quantify methylation quantitative trait loci, the results suggest that cattle CoRSIVs associate with cis-genetic variation
- The surprising finding of higher DNA methylation levels at the 217 sites in one cow compared to the other may derive from the periconceptional environment or a trans-genetic effect during embryonic development
- As in humans, the establishment of DNA methylation at cattle CoRSIVs displays particular sensitivity to the early embryonic environment regarding embryo culture during assisted reproduction (in vitro embryo production vs. multiple ovulation and embryo transfer)
- Overall, genomic regions with systemic interindividual variation in DNA methylation have a generally labile nature in the early embryonic environment
- The following steps in this research will involve expanding the number of cattle, involving additional breeds (some CoRSIVs may display breed-specificity), and improving the depth of WGBS datasets
- The 217 CoRSIVs identified remain comparable in number to the 109 regions detected in an unbiased whole genome bisulfite sequencing screen in humans based on just two individuals carried out by the same team
The team really has hit the bullseye with these DNA methylation-based findings! Overall, exploring CoRSIVs may help develop tools that predict/tailor phenotypic outcomes to boost production efficiency in dairy and beef cattle and perhaps other agriculturally important livestock animals. Importantly, evaluating the methylation status of CoRSIVs in peripheral blood can provide info on epigenetic regulation throughout the body, providing a non-invasive means of analysis.
“Cattle CoRSIVs, like those in people, are established early in life and are stable across the individual’s life,” co-corresponding author Waterland said. “In newborn cattle, methylation patterns across subsets of CoRSIVs may be able to predict future performance. They may be associated with specific desirable traits, like abundant milk production, high female fertility, disease resistance or even heat tolerance, helping select individual calves with traits that will lead to increased productivity.”
For more on how this DNA methylation bullseye may improve livestock farming, see Genome Biology, July 2024.