Studies suggest that a father's experiences such as diet or environmental stress can influence the health and development of his descendants. A paper published today in Nature Communications sheds light on how these effects are transmitted across generations.
In addition to documenting the transmission of epigenetic memory by sperm, the new study shows that the epigenetic information delivered by sperm to the embryo is both necessary and sufficient to guide proper development of germ cells in the offspring.
"We decided to look at C. elegans because it is such a good model for asking epigenetic questions using powerful genetic approaches," said Susan Strome, a distinguished professor of molecular, cell, and developmental biology at University of California - Santa Cruz.
Epigenetic changes do not alter the DNA sequences of genes, but instead involve chemical modifications to either the DNA itself or the histone proteins with which DNA is packaged in the chromosomes. These modifications influence gene expression. The idea that epigenetic modifications can cause changes in gene expression that are transmitted from one generation to the next, known as "transgenerational epigenetic inheritance," is now the focus of intense scientific investigation.
For many years, it was thought that sperm do not retain any histone packaging and therefore could not transmit histone-based epigenetic information to offspring. Recent studies, however, have shown that about 10% of histone packaging is retained in both human and mouse sperm.
"Furthermore, where the chromosomes retain histone packaging of DNA is in developmentally important regions, so those findings raised awareness of the possibility that sperm may transmit important epigenetic information to embryos," Strome said.
When her lab looked at C. elegans sperm, they found the sperm genome fully retains histone packaging. Other researchers had found the same is true for another commonly studied organism, the zebrafish. "Like zebrafish, worms represent an extreme form of histone retention by sperm, which makes them a great system to see if this packaging really matters," Strome said.
Strome’s team found that removing H3K27me3 from sperm chromosomes causes the majority of the offspring to be sterile. Having established that the mark is important, they wanted to see if it is sufficient to guide normal germline development. The researchers addressed this by analyzing a mutant worm in which the chromosomes from sperm and egg are separated in the first cell division after fertilization, so that one cell of the embryo inherits only sperm chromosomes and the other cell inherits only egg chromosomes. This unusual chromosome segregation pattern allowed the researchers to generate worms whose germ line inherited only sperm chromosomes and therefore only sperm epigenetic marks. Those worms turned out to be fertile and to have normal gene expression patterns.
"These findings show that the DNA packaging in sperm is important, because offspring that did not inherit normal sperm epigenetic marks were sterile, and it is sufficient for normal germline development," Strome added.