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

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

doi:10.1038/ncomms13539

Cited by 38 publications

(63 citation statements)

References 55 publications

(89 reference statements)

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“…On the other hand, embryogenesis-related GO terms (such as "morphogenesis of embryonic epithelium" and "negative regulation of transcription from RNApol II promoter") stood out from the list of enriched terms. Thirdly, dMLL3/4 does not regulate the expression of any gene previously associated with the assembly of the zygotic genome [4,26,30]. In particular, all known Drosophila oocyte-toembryo transition genes were expressed at levels similar to controls ( Fig 4C and Dataset EV2).…”

Section: Dmll3/4 Regulates the Expression Of A Functionally Coherent mentioning

confidence: 90%

“…More specifically, by comparing our transcriptomic data with a previously published ribosome footprinting dataset of activated eggs [33], we found that 83 out of the 146 downregulated genes were translated at this transition stage (Fig 4B; Dataset EV1). Thirdly, dMLL3/4 does not regulate the expression of any gene previously associated with the assembly of the zygotic genome [4,26,30]. Accordingly, the gene ontology (GO) analysis of the 83 dMLL3/4-activated genes translated at the oocyte-to-embryo transition failed to detect any enrichment for oogenesis-related processes (such as "female gamete generation" or "female meiosis") [34].…”

Section: Dmll3/4 Regulates the Expression Of A Functionally Coherent mentioning

confidence: 97%

“…To understand why the sperm-borne paternal genome fails to be decondensed in dMLL3/4-depleted eggs, RNAi females were mated with males carrying endogenously fluorescent protamine B (ProtB-GFP) [25]. Protamine B is one of the major nuclear proteins incorporated into sperm chromatin during spermatogenesis, and the formation of the decondensed paternal PN after fertilization requires its active removal (alongside other basic nuclear proteins) from the sperm-borne genome [26]. We observed that the depletion of dMLL3/4 during oogenesis resulted in eggs incapable of ensuring protamine removal after fertilization ( Fig 2B).…”

Section: Dmll3/4 Is Dispensable For Oogenesismentioning

confidence: 99%

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The Trithorax group protein dMLL3/4 instructs the assembly of the zygotic genome at fertilization

et al. 2018

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The transition from fertilized oocyte to totipotent embryo relies on maternal factors that are synthetized and accumulated during oocyte development. Yet, it is unclear how oocytes regulate the expression of maternal genes within the transcriptional program of oogenesis. Here, we report that the Trithorax group protein dMLL3/4 (also known as Trr) is essential for the transition to embryo fate at fertilization. In the absence of dMLL3/4, oocytes develop normally but fail to initiate the embryo mitotic divisions after fertilization. This incapability results from defects in paternal genome reprogramming and maternal meiotic completion. The methyltransferase activity of dMLL3/4 is dispensable for both these processes. We further show that dMLL3/4 promotes the expression of a functionally coherent gene subset that is required for the initiation of post-fertilization development. Accordingly, we identify the evolutionarily conserved IDGF4 glycoprotein (known as oviductin in mammals) as a new oocyte-to-embryo transition gene under direct dMLL3/4 transcriptional control. Based on these observations, we propose that dMLL3/4 plays an instructive role in the oocyte-to-embryo transition that is functionally uncoupled from the requirements of oogenesis.

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Section: Dmll3/4 Regulates the Expression Of A Functionally Coherent mentioning

confidence: 90%

Section: Dmll3/4 Regulates the Expression Of A Functionally Coherent mentioning

confidence: 97%

Section: Dmll3/4 Is Dispensable For Oogenesismentioning

confidence: 99%

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The Trithorax group protein dMLL3/4 instructs the assembly of the zygotic genome at fertilization

et al. 2018

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“…Lastly the pronuclear DNA replication takes place. The general view regarding sperm nucleus decondensation is that the oocyte actively participates in the various steps of this process providing unlocking factors that reduce disulfide bonds, such as the thioredoxin Deadhead recently described in Drosophila (Tirmarche, Kimura, Dubruille, Horard, & Loppin, 2016) and glutathione, similarly acting in mammals (Perreault, Barbee, & Slott, 1988;Sutovsky & Schatten, 1997). In addition the oocyte provides the machinery required for histone modification and incorporation onto the paternal chromatin.…”

Section: Discussionmentioning

confidence: 99%

Involvement of sperm acetylated histones and the nuclear isoform of Glutathione peroxidase 4 in fertilization

Pipolo

Puglisi

Mularoni

et al. 2017

Journal Cellular Physiology

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We previously demonstrated that the nuclear form of Glutathione peroxidase 4 (nGPx4) has a peculiar distribution in sperm head, being localized to nuclear matrix and acrosome and that sperm lacking nGPx4 are more prone to decondensation in vitro. In this study we have hypothesized that sperm retained acetylated histones and nGPx4 are implicated in paternal chromatin decondensation and male pronucleus formation at fertilization. Indeed, significant higher amounts of acetylated histone H4 and acetylated histone H3 were observed by both immunofluorescence and western blotting in nGPx4-KO sperm vs WT ones. In vitro fertilization of zona pellucida-deprived oocytes by WT sperm in the presence of trichostatin (TSA) also demonstrated that paternal histone acetylation was inversely related to the timing of sperm nucleus decondensation at fertilization. In contrast, TSA had no effect on nGPx4-KO sperm, indicating they had a maximal level of histone acetylation. Moreover the paternally imprinted gene Igf2/H19 was hypomethylated in KO sperm compared to WT ones. The lack of nGPx4 negatively affected male fertility, causing a marked decrease in total pups and pregnancies with delivery, a significant reduction in pronuclei (PN) embryos in in vitro fertilization assays and an approximately 2 h delay in egg fertilization in vivo. Because the zona pellucida binding and fusion to oolemma of nGPx4-KO and WT sperm were similar, the subfertility of nGPx4 sperm reflected a decreased sperm progression through egg cumulus/zona pellucida, pinpointing a defective acrosome in line with acrosomal nGPx4 localization. We conclude that paternal acetylated histones and acrosomal nGPx4 are directly involved in fertilization.

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“…In addition, paternal DNA must be de-compacted after fertilization, meaning that sperm nucleotide binding proteins must be degraded 89 . The enzymes/proteins that participate in this process are likely already present in the egg, and therefore maternally contributed 90 . This is followed by histone/chromatin assembly which is dependent on maternally provided histones and nucleosome assembly factors 90,91 .…”

Section: Belgicamentioning

confidence: 99%

Multi-level analysis of reproduction in the Antarctic midge,Belgica antarctica, identifies female and male accessory gland products that are altered by larval stress and impact progeny viability

Finch

Perrieta

Davis

et al. 2019

Preprint

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Background -The Antarctic midge, Belgica antarctica, is a wingless, non-biting midge endemic to Antarctica. Larval development requires at least two years, but adult life lasts only two weeks. The nonfeeding adults mate in swarms and females die shortly after oviposition. Eggs are suspended in a gel of unknown composition that is expressed from the female accessory gland. This project characterizes molecular mechanisms underlying reproduction in this midge by examining differential gene expression in whole males, females, and larvae, as well as in male and female accessory glands. Functional studies were used to assess the role of the gel encasing the eggs, as well as the impact of stress on reproductive biology.Results -RNA-seq analyses revealed sex-and development-specific gene sets along with those associated with the accessory glands. Proteomic analyses were used to define the composition of the egg-containing gel, which is generated during multiple developmental stages and derived from both the accessory gland and other female organs. Functional studies indicate the gel provides a larval food source and thermal and dehydration buffer, all of which are critical for viability. Larval dehydration stress directly reduces production of storage proteins and key accessory gland components, a feature that impacts adult reproductive success. Modeling reveals that bouts of dehydration may significantly impact population growth. Conclusions -This work lays a foundation for further examination of reproduction in midges andprovides new information related to general reproduction in dipterans. A key aspect is that reproduction and stress dynamics, currently understudied in polar organisms, are likely to prove critical for determining how climate change will alter survivability.

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

Cited by 38 publications

References 55 publications

The Trithorax group protein dMLL3/4 instructs the assembly of the zygotic genome at fertilization

The Trithorax group protein dMLL3/4 instructs the assembly of the zygotic genome at fertilization

Involvement of sperm acetylated histones and the nuclear isoform of Glutathione peroxidase 4 in fertilization

Multi-level analysis of reproduction in the Antarctic midge,Belgica antarctica, identifies female and male accessory gland products that are altered by larval stress and impact progeny viability

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