Unlocking sperm chromatin at fertilization requires a dedicated egg thioredoxin in Drosophila.

Samantha Tirmarche,Raphaëlle Dubruille,Benjamin Loppin,Béatrice Horard,Shuhei Kimura

doi:10.1038/ncomms13539

Samantha Tirmarche, Raphaëlle Dubruille + Show 3 more

Open Access

https://doi.org/10.1038/ncomms13539

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Abstract

In most animals, the extreme compaction of sperm DNA is achieved after the massive replacement of histones with sperm nuclear basic proteins (SNBPs), such as protamines. In some species, the ultracompact sperm chromatin is stabilized by a network of disulfide bonds connecting cysteine residues present in SNBPs. Studies in mammals have established that the reduction of these disulfide crosslinks at fertilization is required for sperm nuclear decondensation and the formation of the male pronucleus. Here, we show that the Drosophila maternal thioredoxin Deadhead (DHD) is specifically required to unlock sperm chromatin at fertilization. In dhd mutant eggs, the sperm nucleus fails to decondense and the replacement of SNBPs with maternally-provided histones is severely delayed, thus preventing the participation of paternal chromosomes in embryo development. We demonstrate that DHD localizes to the sperm nucleus to reduce its disulfide targets and is then rapidly degraded after fertilization.

Highlights

In most animals, the extreme compaction of sperm DNA is achieved after the massive replacement of histones with sperm nuclear basic proteins (SNBPs), such as protamines
In this study, we have identified the Drosophila maternal thioredoxin Deadhead as critically required for sperm nuclear decondensation at fertilization
We propose that DHD is involved in the reduction of disulfide crosslinks that connect cysteine residues of SNBPs in mature sperm chromatin

Summary

Discussion

We have identified the Drosophila maternal thioredoxin Deadhead as critically required for sperm nuclear decondensation at fertilization. We propose that DHD is involved in the reduction of disulfide crosslinks that connect cysteine residues of SNBPs in mature sperm chromatin. We first established that Drosophila sperm chromatin, which is packaged with cysteinerich SNBPs, is stabilized by disulfide crosslinks. Little is known about the structural organization of Drosophila sperm chromatin, a recent study showed that the Drosophila SNBP Mst77F is a DNA binding protein which induces DNA condensation in vitro through a multimerization process involving its coiled-coil domain[45]. The implication of DHD in the reduction of sperm chromatin disulfide crosslinks in Drosophila eggs is first supported by our detailed characterization of the dhd phenotype. Among the rare Drosophila maternal effect mutants affecting sperm chromatin remodelling[33,34,46], dhd is unique and shows the earliest phenotype reported so far. Any role of DHD in the reduction of c w 1118 a

C DHD α-Tubulin

Findings

Methods