Histone removal in sperm protects paternal chromosomes from premature division at fertilization

Abstract

The global replacement of histones with protamines in sperm chromatin is widespread in animals, including insects, but its actual function remains enigmatic. We show that in the Drosophila paternal effect mutant paternal loss ( pal ), sperm chromatin retains germline histones H3 and H4 genome wide without impairing sperm viability. However, after fertilization, pal sperm chromosomes are targeted by the egg chromosomal passenger complex and engage into a catastrophic premature division in synchrony with female meiosis II. We show that pal encodes a rapidly evolving transition protein specifically required for the eviction of (H3-H4) 2 tetramers from spermatid DNA after the removal of H2A-H2B dimers. Our study thus reveals an unsuspected role of histone eviction from insect sperm chromatin: safeguarding the integrity of the male pronucleus during female meiosis.

The protamines of the noble false widow spiderSteatoda nobilisprovide an example of liquid-liquid phase separation chromatin transitions during spermiogenesis

“…In the functional regard, protamines have recently gained a lot of attention. In the case of invertebrate protamines, the protamine-mediated removal of histones in the sperm of Drosophila (Rathke et al, 2014) has been shown to protect paternal chromosomes from premature division at fertilization (Dubruille et al, 2023). In mice, it has been shown that despite these protamines’ seemingly monotonous arginine composition, substituting a single lysine in protamine 1 in this vertebrate results in sperm chromatin and reproductive fitness alterations (Moritz et al, 2023).…”