Multimerization of Drosophila sperm protein Mst77F causes a unique condensed chromatin structure

Kost, Nils; Kaiser, Sophie; Ostwal, Yogesh B.; Riedel, Dietmar; Stützer, Alexandra; Nikolov, Miroslav; Rathke, Christina; Renkawitz‐Pohl, Renate; Fischle, Wolfgang

doi:10.1093/nar/gkv015

Cited by 16 publications

(29 citation statements)

References 50 publications

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“…This is a strong indication that these residues are indeed important for the function of mature Mst77F, presumably through their ability to form disulfide bonds. In vitro , Mst77F was shown to interact with DNA with its C-terminal domain, which triggered in turn the multimerization of the protein via the N-terminus domain, eventually forming protein–DNA aggregates [29]. If this model holds true in vivo , we speculate that the putative N-terminal multimerization domain could be eliminated by proteolysis after Mst77F deposition and its subsequent stabilization with intermolecular disulfide bonds (figure 7).…”

Section: Discussionmentioning

confidence: 98%

“…(i) Mst77F (yellow ovals) first binds DNA through its C-terminus as proposed by Kost et al . [29]. (ii) DNA-bound Mst77F proteins multimerize through N-terminus interactions [29].…”

Section: Discussionmentioning

confidence: 99%

“…A legitimate concern with these conclusions is that they were essentially based on the analysis of a single point mutant allele of Mst77F that apparently behaved as an antimorph [11,24]. Furthermore, a recent study provided evidence that Mst77F had the ability to efficiently aggregate DNA in vitro , suggesting that the protein could play a role in sperm nuclear compaction rather than nuclear shaping [29]. …”

Section: Introductionmentioning

confidence: 99%

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TheDrosophilachromosomal protein Mst77F is processed to generate an essential component of mature sperm chromatin

Kimura¹,

Loppin²

2016

Open Biol.

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In most animals, the bulk of sperm DNA is packaged with sperm nuclear basic proteins (SNBPs), a diverse group of highly basic chromosomal proteins notably comprising mammalian protamines. The replacement of histones with SNBPs during spermiogenesis allows sperm DNA to reach an extreme level of compaction, but little is known about how SNBPs actually function in vivo. Mst77F is a Drosophila SNBP with unique DNA condensation properties in vitro, but its role during spermiogenesis remains unclear. Here, we show that Mst77F is required for the compaction of sperm DNA and the production of mature sperm, through its cooperation with protamine-like proteins Mst35Ba/b. We demonstrate that Mst77F is incorporated in spermatid chromatin as a precursor protein, which is subsequently processed through the proteolysis of its N-terminus. The cleavage of Mst77F is very similar to the processing of protamine P2 during human spermiogenesis and notably leaves the cysteine residues in the mature protein intact, suggesting that they participate in the formation of disulfide cross-links. Despite the rapid evolution of SNBPs, sperm chromatin condensation thus involves remarkably convergent mechanisms in distantly related animals.

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Section: Discussionmentioning

confidence: 98%

“…(i) Mst77F (yellow ovals) first binds DNA through its C-terminus as proposed by Kost et al . [29]. (ii) DNA-bound Mst77F proteins multimerize through N-terminus interactions [29].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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TheDrosophilachromosomal protein Mst77F is processed to generate an essential component of mature sperm chromatin

Kimura¹,

Loppin²

2016

Open Biol.

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“…Similarly, it has been recently shown that pre-treatment of Drosophila sperm nuclei with DTT improves antibody accessibility to nuclear epitopes in immunofluorescence experiments32. Although 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 domain45. Oxidation of cysteine thiols present in Mst77F could participate in the stabilization of this unique chromatin architecture through the establishment of disulfide crosslinks.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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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.

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“…In addition, Mst77F, a protein similar to the linker histone H1, is also found in mature sperm [5]. Mst77F is specifically expressed post-meiotically and interacts with DNA, causing major condensation of the chromatin [8]. Mst77F also coordinates microtubules during nuclear shaping when sperm heads change from spherical to needle shaped with condensed chromatin [5].…”

mentioning

confidence: 99%

Versager is expressed at the histone-to-protamine transition during spermiogenesis and is required for embryonic chromosome transmission in Drosophila melanogaster

Binder¹,

Wakimoto²,

Davis³

et al. 2017

Res J Dev Biol

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Background: Chromatin remodeling is one of the most intriguing features of spermiogenesis, during which nuclei undergo drastic morphological changes leading to extensive chromatin compaction. Genetic and cytological accessibility make Drosophila melanogaster a powerful model to study this process. In fruit flies, paternal histones are largely replaced with sperm specific nuclear basic proteins in a highly coordinated manner. This remodeling is essential not only for sperm function but also for proper behavior of paternal chromosomes in the embryo. Our understanding of the changes associated with sperm chromatin and their role in embryonic chromosome behavior is incomplete, and will depend on the identification and characterization of additional components. One such newly identified gene, versager (vrs), is described here. Methods: Chromosome transmission was genetically monitored from vrs Z2566 males using chromosomespecific visible mutations. Recombination and deletion mapping was used to localize the mutation, and DNA sequencing was used to identify the causative lesion. Both in vivo RNAi expression knockdown and rescue by transgene expression of EGFP-tagged protein were used to verify the gene identity. The developmental expression pattern of Vrs was defined based on the EGFP signal in testis relative to RFP-tagged H2Av expression. Behavior of DAPI-stained chromosomes in early embryos from vrs Z2566 males was examined using confocal microscopy. Results: Genetic observations indicated that vrsZ2566 is required in males for high fidelity transmission of paternally derived chromosomes. DNA sequencing revealed that the vrs Z2566 mutation is a missense mutation in Celera predicted gene CG5538 and results in a D2V amino acid substitution. This residue was found to be conserved in Drosophila species and related Diptera. RNAi knockdown of vrs resulted in paternal-effect chromosome loss, and a vrs + -EGFP transgene fully rescued the mutant phenotype. Confocal microscopy of testis revealed nuclear localization of Vrs-EGFP specifically at the canoe stage of spermiogenesis, overlapping with the time of removal of H2Av-RFP at the histone-to-protamine transition. Examination of early stage embryos revealed micronuclei, isolated chromosomes and bridges indicative of chromosome loss events during the first three divisions. Approximately a quarter of later stage embryos arrested with an abnormal number of metaphase and fragmented nuclei. Conclusions: A novel sperm-specific paternal-effect gene, vrs, was identified that is expressed at the histone-to-protamine transition and is important for embryonic chromosome behavior and development. The histone-to-protamine transition may be a developmental period sensitive to perturbations that may lead to embryonic mitotic errors, aneuploidy and developmental arrest.

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Multimerization of Drosophila sperm protein Mst77F causes a unique condensed chromatin structure

Cited by 16 publications

References 50 publications

TheDrosophilachromosomal protein Mst77F is processed to generate an essential component of mature sperm chromatin

TheDrosophilachromosomal protein Mst77F is processed to generate an essential component of mature sperm chromatin

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

Versager is expressed at the histone-to-protamine transition during spermiogenesis and is required for embryonic chromosome transmission in Drosophila melanogaster

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