Most of us wouldn’t mind taking a tropical vacation, and we’re all likely to snap a few selfies to capture vacation memories. While the humble Caenorhabditis elegans may lack the latest phone and accompanying selfie stick, it makes up for it with epigenetic memory of warm weather vacations. More specifically, worms raised at higher temperatures undergo epigenetic changes which are retained in future generations—even when moved back to lower temperatures.
Rather than taking a vacation, researchers from the labs of Ben Lehner (European Molecular Biology Laboratory) and Tanya Vavouri (Josep Carreras Leukaemia Research Institute) have been hard at work investigating transgenerational epigenetic inheritance. Their recent work has uncovered the transmission of environmentally induced epigenetic changes that persist for 14 generations in C. elegans.
The talented team took C. elegans and integrated a multicopy transgene coding for a fluorescent protein. The transgene was put under the control of the daf-21 promoter (hsp90) so that increased temperature would drive expression. The worms were then subjected to a Bahamas-worthy 25oC for five consecutive generations. Subsequent generations of worms were raised at 20oC, and expression from the transgene was assessed:
- Expression of the transgene was elevated for 14 generations after the return to 20oC
- Worms whose ancestors were grown at higher temperatures exhibit differential histone modification
- Progeny have decreased trimethylation on histone 3, lysine 9 (H3K9me3)—a modification associated with repression
- SET-25 is the methyltransferase responsible for H3K9 trimethylation, and is required for repression at low temperatures
- Inactivation of set-25resulted in increased expression of the transgene—expression was equivalent in worms raised at either 20oC or 25oC
- For endogenous loci, repetitive elements and pseudogenes were most affected by SET-25 derepression
- Although changes in endogenous protein-coding genes were minor, they were detectable for three generations after being returned to the low-temperature environment
Thus, it appears that high temperature (25oC) inhibits the SET-25 pathway, leading to loss of methylation at H3K9, resulting in increased expression from the transgene array. This change in chromatin state is transmitted to progeny, resulting in an epigenetic “memory” of the high-temperature environment. The repression is restored via heterochromatin remodeling during normal cell division through subsequent generations.
Co-senior author Ben Lehner shares, “We discovered this phenomenon by chance, but it shows that it’s certainly possible to transmit information about the environment down the generations.” First author Adam Klosin adds, “We don’t know exactly why this happens, but it might be a form of biological forward-planning.” Co-senior author Tanya Vavouri concludes, “Worms are very short-lived, so perhaps they are transmitting memories of past conditions to help their descendants predict what their environment might be like in the future.”
Although the inheritance of epigenetic alterations is not a new phenomenon, the persistence over 14 generations raises new questions about the potential duration of epigenetic inheritance. Just to be safe, for the sake of your great-great-grandchildren, go ahead and take a tropical vacation.
Take a tropical vacation over at Science, 2017