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

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. , Editor’s summary Ultracompaction of sperm DNA in many species is often associated with genome-wide replacement of histones with protamines, but the actual role of this radical change in chromatin organization remains largely enigmatic. Looking at a multidecade-old Drosophila mutant, Dubruille et al . found that histones were massively retained in sperm without affecting its ability to fertilize (see the Perspective by Levine). However, at fertilization, male chromosomes were aberrantly recognized by maternal factors that control female meiotic progression, leading to a deleterious premature division and early loss of male chromosomes. This work highlights the role of sperm chromatin in protecting male chromosomes in the egg. —Di Jiang , Histone retention in Drosophila sperm chromatin jeopardizes paternal chromosome integrity during female meiosis.