The Lid/KDM5 histone demethylase complex activates a critical effector of the oocyte-to-zygote transition

Torres-Campana, Daniela; Kimura, Shuhei; Orsi, Guillermo A.; Horard, Béatrice; Galand, Benoît; Loppin, Benjamin

doi:10.1371/journal.pgen.1008543

Cited by 11 publications

(19 citation statements)

References 41 publications

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“…key regulators, such as GNU, LID and DHD, exhibit protein level patterns that are consistent with their functions during the transition (Torres-Campana et al 2020;Kronja et al 2014a;Petrova et al 2018). Similar to these proteins, many other proteins show protein level patterns suggestive of developmental control (Kronja et al 2014a).…”

Section: Discussionmentioning

confidence: 70%

Identification of New Regulators of the Oocyte-to-Embryo Transition inDrosophila

Avilés-Pagán

Kang

Orr‐Weaver

2020

G3 Genes|Genomes|Genetics

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At the oocyte-to-embryo transition the highly differentiated oocyte arrested in meiosis becomes a totipotent embryo capable of embryogenesis. Oocyte maturation (release of the prophase I primary arrest) and egg activation (release from the secondary meiotic arrest and the trigger for the oocyte-to-embryo transition) serve as prerequisites for this transition, both events being controlled posttranscriptionally. Recently, we obtained a comprehensive list of proteins whose levels are developmentally regulated during these events via a high-throughput quantitative proteomic analysis of Drosophila melanogaster oocyte maturation and egg activation. We conducted a targeted screen for potential novel regulators of the oocyte-to-embryo transition, selecting 53 candidates from these proteins. We reduced the function of each candidate gene using transposable element insertion alleles and RNAi, and screened for defects in oocyte maturation or early embryogenesis. Deletion of the aquaporin gene CG7777 did not affect female fertility. However, we identified CG5003 and nebu (CG10960) as new regulators of the transition from oocyte to embryo. Mutations in CG5003, which encodes an F-box protein associated with SCF-proteasome degradation function, cause a decrease in female fertility and early embryonic arrest. Mutations in nebu, encoding a putative glucose transporter, result in defects during the early embryonic divisions, as well as a developmental delay and arrest. nebu mutants also exhibit a defect in glycogen accumulation during late oogenesis. Our findings highlight potential previously unknown roles for the ubiquitin protein degradation pathway and sugar transport across membranes during this time, and paint a broader picture of the underlying requirements of the oocyte-to-embryo transition.

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Section: Discussionmentioning

confidence: 70%

Identification of New Regulators of the Oocyte-to-Embryo Transition inDrosophila

Avilés-Pagán

Kang

Orr‐Weaver

2020

G3 Genes|Genomes|Genetics

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“…We previously showed that H3K4me3, a histone modification associated with active transcription, is enriched at the dhd promoter and that this mark is lost in lid KD ovaries [5](FigS2-A). Further exploiting published ChIP-seq datasets, we surprisingly found that dhd lies within a ∼5kbp mini-domain featuring two types of repressive histone modifications: H3K27me3 and H3K9me3 [24, 25].…”

Section: Resultsmentioning

confidence: 99%

“…Understanding their function therefore requires identifying biologically relevant situations where disrupting these effectors impacts transcription in a critical and specific manner. We previously described one of such cases, where perturbation of the histone demethylase Lid/KDM5 or the histone deacetylase scaffold Sin3A in Drosophila ovaries dramatically abrogated the expression of the essential maternal gene deadhead (dhd) [5].…”

Section: Introductionmentioning

confidence: 99%

“…The Drosophila egg is loaded with maternal gene products synthesized by germline nurse cells that enable early embryonic development in the absence of zygotic transcription [6]. An extreme example of this specialized transcriptome, dhd is among the most highly expressed genes in adult ovaries, while it is almost completely silent in any other tissue and developmental stage [5,[7][8][9]. The DHD protein is a thioredoxin involved in regulating the general redox state in oocytes [10].…”

Section: Introductionmentioning

confidence: 99%

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Three classes of epigenomic regulators converge to hyperactivate the essential maternal gene deadhead within a heterochromatin mini-domain

Torres-Campana

Horard

Denaud

et al. 2021

Preprint

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The formation of a diploid zygote is a highly complex cellular process that is entirely controlled by maternal gene products stored in the egg cytoplasm. This highly specialized transcriptional program is tightly controlled at the chromatin level in the female germline. As an extreme case in point, the massive and specific ovarian expression of the essential thioredoxin Deadhead (DHD) is critically regulated in Drosophila by the histone demethylase Lid and its partner, the histone deacetylase complex scaffold Sin3A, via yet unknown mechanisms. Here, we identified the Brahma chromatin remodeler sub-unit Snr1 and the insulator component Mod(mdg4) as essential for dhd expression and investigated how these epigenomic effectors act with Lid and Sin3A to hyperactivate dhd . Using Cut&Run chromatin profiling with a dedicated data analysis procedure, we found that dhd is intriguingly embedded in an H3K27me3/H3K9me3-enriched mini-domain flanked by DNA regulatory elements, including a dhd promoter-proximal element essential for its expression. Surprisingly, Lid, Sin3A, Snr1 and Mod(mdg4) impact H3K27me3 and this regulatory element in distinct manners. However, we show that these effectors activate dhd independently of H3K27me3/H3K9me3, and that these marks are not required to repress dhd . Together, our study demonstrates an atypical and critical role for chromatin regulators Lid, Sin3A, Snr1 and Mod(mdg4) to trigger tissue-specific hyperactivation within a unique heterochromatin mini-domain.

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“…Moreover, Dhd plays crucial roles in the oocyte-to-embryo transition, where it reduces and modulates the activity of ribosomal and RNA-binding proteins, as well as that of the histone demethylase NO66 (Petrova et al, 2018). Recently, the transcriptional regulation of Dhd has been reported to be modulated by the lysinespecific demethylase 5 (KDM5), a potent chromatin remodeler during female gametogenesis (Torres-Campana et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Structures of the germline-specific Deadhead and thioredoxin T proteins fromDrosophila melanogasterreveal unique features among thioredoxins

Freier¹,

Aragón²,

Bagiński³

et al. 2021

IUCrJ

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Thioredoxins (Trxs) are ubiquitous enzymes that regulate the redox state in cells. In Drosophila, there are two germline-specific Trxs, Deadhead (Dhd) and thioredoxin T (TrxT), that belong to the lethal(3)malignant brain tumor signature genes and to the `survival network' of genes that mediate the cellular response to DNA damage. Dhd is a maternal protein required for early embryogenesis that promotes protamine–histone exchange in fertilized eggs and midblastula transition. TrxT is testis-specific and associates with the lampbrush loops of the Y chromosome. Here, the first structures of Dhd and TrxT are presented, unveiling new features of these two thioredoxins. Dhd has positively charged patches on its surface, in contrast to the negatively charged surfaces commonly found in most Trxs. This distinctive charge distribution helps to define initial encounter complexes with DNA/RNA that will lead to final specific interactions with cofactors to promote chromatin remodeling. TrxT contains a C-terminal extension, which is mostly unstructured and highly flexible, that wraps the conserved core through a closed conformation. It is believed that these new structures can guide future work aimed at understanding embryo development and redox homeostasis in Drosophila. Moreover, due to their restricted presence in Schizophora (a section of the true flies), these structures can help in the design of small-molecular binders to modulate native redox homeostasis, thereby providing new applications for the control of plagues that cause human diseases and/or bring about economic losses by damaging crop production.

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The Lid/KDM5 histone demethylase complex activates a critical effector of the oocyte-to-zygote transition

Cited by 11 publications

References 41 publications

Identification of New Regulators of the Oocyte-to-Embryo Transition inDrosophila

Identification of New Regulators of the Oocyte-to-Embryo Transition inDrosophila

Three classes of epigenomic regulators converge to hyperactivate the essential maternal gene deadhead within a heterochromatin mini-domain

Structures of the germline-specific Deadhead and thioredoxin T proteins fromDrosophila melanogasterreveal unique features among thioredoxins

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