In the game of transgenerational epigenetic inheritance, many labs have been searching for a slam dunk. Now, in a game-changing new article, ballers from the laboratory of Michael K. Skinner (Washington State University, Pullman, WA, USA) provide a play-by-play of how teamwork between non-coding RNA expression, DNA methylation, and histone modifications allows rat sperm to throw epigenetic “three-pointers” that mediate transgenerational epigenetic inheritance following exposure to environmental stressors. Let’s head to the tip-off!
The talented team previously described the transgenerational inheritance of three layers of epigenetic modifications following exposure to environmental stressors such as the pesticide DDT (dichloro-diphenyl-trichloroethane) or the agricultural toxicant vinclozolin. Now, the authors hit the court to discover whether non-coding RNA expression, DNA methylation, and histone modifications could truly work together as a team and beat the buzzer with a game-winning shot.
So, what did Beck and colleagues discover from their flexible strategic analysis of gestating rat females transiently exposed to vinclozolin or DDT? Did teamwork make the dream work?
- A significant degree of genomic colocalization exists between non-coding RNA expression, differentially-DNA methylated regions, and areas of differential-histone retention in sperm isolated from later generations of male offspring (F1-3)
- Fascinatingly, the F1 sperm non-coding RNA expression profile significantly overlaps the differentially-DNA methylated regions present in the F1, F2, and F3 offspring, thereby suggesting a role for RNA-directed DNA methylation
- Additionally, the RNA-directed differentially-DNA methylated regions also overlap with areas of differential-histone retention, thereby also suggesting the existence of a DNA methylation-directed histone retention program
While James Harden´s move to the Nets may ruffle a few more feathers in the basketball world, this game-changing new study does suggest that three-pointers may represent the best epigenetic play when mammals are faced with the daunting task of passing down potentially vital information to their offspring. However, the authors note that many epigenetic elements do not team-up and underscore the importance of understanding independent epigenetic “plays” in environmentally-induced epigenetic transgenerational inheritance.