While Instagram may have replaced the Polaroid, some age-old memories just can’t be shaken. Thankfully, the sperm epigenome of C. elegans has conjured up the latest social media trend, the histonagram: a histone based memory of spermatogenesis and oogenesis that shapes offspring fertility.
Although C. elegans differ from us humans in that they don’t make use of DNA cytosine methylation, they do share an important similarity to us: the incomplete replacement of histones by protamines. The retention of histones, and their post-translational modifications, serves as a crucial mechanism for the transmission of epigenetic information. To shed light on the mechanisms of paternal transmission and nucleosome retention in C. elegans sperm, the lab of Susan Strome at the University of California, Santa Cruz captured some of the most striking histonagrams yet.
Here’s what they captured:
- Micrococcal nuclease digestion followed by sequencing (MNase-seq) and ChIP-seq revealed that elegans sperm retain nucleosomes genome-wide, where H3K36me3 and H3K27me3 tend to occupy mutually exclusive regions
- Genes expressed during spermatogenesis, but not in mature sperm or embryos, display a unique multivalent chromatin signature consisting of active (H3K36me3 and H3K4me3) and repressive (H3K27me3) marks
- Surprisingly, oogenesis genes typically do not exhibit repressive marks (H3K27me3), but instead display active histone marks (H3K36me3 and H3K4me3) in sperm
- These genes are actively transcribed in sperm
- By focusing on a mutant strain lacking H3K27me3, the team observed that sperm chromatin transmits epigenetic information
- This process is crucial for the germline development of resulting offspring, as a large number of offspring from mutant fathers suffer from sterility
- Making use of a mutant background that generates mosaics whose germlines derive from only sperm chromosomes, the group established that sperm chromatin on its own can generate fertile offspring
Senior author Susan Strome shares, “We decided to look at C. elegans because it is such a good model for asking epigenetic questions using powerful genetic approaches. 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. 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.
“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. The goal is to analyze how the chromatin packaging changes in the parent. Whatever gets passed on to the offspring has to go through the germ cells. We want to know which cells experience the environmental factors, how they transmit that information to the germ cells, what changes in the germ cells, and how that impacts the offspring.”
Overall, while mammalian sperm maintainsonly 1-10% of nucleosomes, their presence and similar multivalent markings alongside their functional differences suggestthat histonagrams from the humble nematode may have more to offer than meets the eye.