A global expression switch marks pachytene initiation during mouse male meiosis
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Philippe Bois
PROVIDER: E-GEOD-21447 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Male spermatogenesis is an essential and complex developmental process with the purpose to gain totipotency and allow a whole new organism to develop upon fertilization. While single-gene based studies have provided insights into the mechanisms at work, global profiling is clearly required to deconvolute these processes. Here, by isolating highly enriched mouse meiotic cell populations, we report a comprehensive gene expression map of mammalian meiosis. Our data reveal in unique details the dynamic of fundamental expression patterns such as the global chromosome X inactivation and reactivation allowing to precisely dissect this unique process. It also reveals a rapid global expression switch at the initiation of the long pachytene stage reminiscent and coincident with the commitment to meiosis observed in budding yeast. Overall, this meiotic atlas provides an exhaustive blueprint and resource for deconvoluting mammalian gametogenesis and meiosis.
2010-12-16 | GSE21447 | GEO
Project description:During embryonic germ cell development in mice, transposon-enriched, piwi-interacting RNAs (piRNAs) guide MILI and MIWI2 to direct silencing of potentially active mobile element families. In contrast, we know much less about the function of the highly abundant and extremely diverse class of piRNAs, which partner with MIWI and MILI during meiosis. Both MIWI and its catalytic activity are required for successful spermatogenesis, strongly indicating that piRNA-guided cleavage is critical for germ cell development. To gain an understanding of meiotic piRNA targets, we augmented the mouse piRNA repertoire by introducing an entire human meiotic piRNA cluster. This triggered a spermatogenesis defect, presumably by inappropriately targeting the piRNA machinery to mouse RNAs essential for germ cell development. Through an analysis of such de novo targets, we derived a signature for pachytene piRNA target recognition. This enabled identification of both transposable elements and meiotically expressed protein coding genes as targets of native piRNAs. Cleavage of genic targets begins at the pachytene stage when meiotic piRNAs first appear. As such, target mRNA levels attenuate starting from the pachytene stage and are further repressed throughout meiosis. Target mRNA-piRNA pairs also show evidence of an ongoing cleavage-dependent amplification cycle, which is not normally a strong feature of meiotic piRNAs. Our data support the idea that meiotic piRNA populations must be strongly selected to enable successful spermatogenesis, both driving the response away from essential genes and directing the pathway toward mRNA targets that are regulated by small RNAs in meiotic cells. 48 samples
2015-05-22 | E-GEOD-64138 | biostudies-arrayexpress
Project description:During embryonic germ cell development in mice, transposon-enriched, piwi-interacting RNAs (piRNAs) guide MILI and MIWI2 to direct silencing of potentially active mobile element families. In contrast, we know much less about the function of the highly abundant and extremely diverse class of piRNAs, which partner with MIWI and MILI during meiosis. Both MIWI and its catalytic activity are required for successful spermatogenesis, strongly indicating that piRNA-guided cleavage is critical for germ cell development. To gain an understanding of meiotic piRNA targets, we augmented the mouse piRNA repertoire by introducing an entire human meiotic piRNA cluster. This triggered a spermatogenesis defect, presumably by inappropriately targeting the piRNA machinery to mouse RNAs essential for germ cell development. Through an analysis of such de novo targets, we derived a signature for pachytene piRNA target recognition. This enabled identification of both transposable elements and meiotically expressed protein coding genes as targets of native piRNAs. Cleavage of genic targets begins at the pachytene stage when meiotic piRNAs first appear. As such, target mRNA levels attenuate starting from the pachytene stage and are further repressed throughout meiosis. Target mRNA-piRNA pairs also show evidence of an ongoing cleavage-dependent amplification cycle, which is not normally a strong feature of meiotic piRNAs. Our data support the idea that meiotic piRNA populations must be strongly selected to enable successful spermatogenesis, both driving the response away from essential genes and directing the pathway toward mRNA targets that are regulated by small RNAs in meiotic cells.
2015-05-22 | GSE64138 | GEO
Project description:Meiosis is the specialized cell division during which parental genomes recombine to create genotypically unique gametes. Despite its importance, mammalian meiosis cannot be studied in vitro, greatly limiting mechanistic studies. In vivo, meiocytes progress asynchronously through meiosis and therefore the study of specific stages of meiosis is a challenge. Here, we describe a simple method for isolating pure sub-populations of meiocytes that allows for detailed study of meiotic sub-stages. Interrogating the H3K4me3 landscape revealed dynamic chromatin transitions between sub-stages of meiotic prophase I, both at sites of genetic recombination and at gene promoters. We also leveraged this method to perform the first comprehensive, genome-wide survey of histone marks in meiotic prophase, revealing a heretofore unappreciated complexity of the epigenetic landscape at meiotic recombination hotspots. Ultimately, this study presents a simple, scalable framework for interrogating the complexities of mammalian meiosis.
2019-07-31 | GSE121760 | GEO
Project description:Germ cells manifest a unique gene expression program and regain totipotency in the zygote. Here, we perform Hi-C analysis to examine 3D chromatin organization in male germ cells during spermatogenesis. We show that the highly compartmentalized 3D chromatin organization characteristic of interphase nuclei is attenuated in meiotic prophase. Meiotic prophase is predominated by short-range intrachromosomal interactions that represent a condensed form akin to that of mitotic chromosomes. However, unlike mitotic chromosomes, meiotic chromosomes display weak genomic compartmentalization, weak topologically associating domains, and localized point interactions in prophase. In postmeiotic round spermatids, genomic compartmentalization increases and gives rise to the strong compartmentalization seen in mature sperm. The X chromosome lacks domain organization during meiotic sex-chromosome inactivation. We propose that male meiosis occurs amid global reprogramming of 3D chromatin organization and that strengthening of chromatin compartmentalization takes place in spermiogenesis to prepare the next generation of life.
2019-02-18 | GSE119805 | GEO
Project description:Ray2013 - Meiotic initiation in S. cerevisiae
A mathematical representation of early meiotic events, particularly feedback mechanisms at the system level and phosphorylation of signalling molecules for regulating protein activities, is described here
This model is described in the article:
Dynamic modeling of yeast meiotic initiation.
Ray D, Su Y, Ye P.
BMC Syst Biol. 2013 May 1;7:37
Abstract:
BACKGROUND:
Meiosis is the sexual reproduction process common to eukaryotes. The diploid yeast Saccharomyces cerevisiae undergoes meiosis in sporulation medium to form four haploid spores. Initiation of the process is tightly controlled by intricate networks of positive and negative feedback loops. Intriguingly, expression of early meiotic proteins occurs within a narrow time window. Further, sporulation efficiency is strikingly different for yeast strains with distinct mutations or genetic backgrounds. To investigate signal transduction pathways that regulate transient protein expression and sporulation efficiency, we develop a mathematical model using ordinary differential equations. The model describes early meiotic events, particularly feedback mechanisms at the system level and phosphorylation of signaling molecules for regulating protein activities.
RESULTS:
The mathematical model is capable of simulating the orderly and transient dynamics of meiotic proteins including Ime1, the master regulator of meiotic initiation, and Ime2, a kinase encoded by an early gene. The model is validated by quantitative sporulation phenotypes of single-gene knockouts. Thus, we can use the model to make novel predictions on the cooperation between proteins in the signaling pathway. Virtual perturbations on feedback loops suggest that both positive and negative feedback loops are required to terminate expression of early meiotic proteins. Bifurcation analyses on feedback loops indicate that multiple feedback loops are coordinated to modulate sporulation efficiency. In particular, positive auto-regulation of Ime2 produces a bistable system with a normal meiotic state and a more efficient meiotic state.
CONCLUSIONS:
By systematically scanning through feedback loops in the mathematical model, we demonstrate that, in yeast, the decisions to terminate protein expression and to sporulate at different efficiencies stem from feedback signals toward the master regulator Ime1 and the early meiotic protein Ime2. We argue that the architecture of meiotic initiation pathway generates a robust mechanism that assures a rapid and complete transition into meiosis. This type of systems-level regulation is a commonly used mechanism controlling developmental programs in yeast and other organisms. Our mathematical model uncovers key regulations that can be manipulated to enhance sporulation efficiency, an important first step in the development of new strategies for producing gametes with high quality and quantity.
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2017-02-03 | BIOMD0000000626 | BioModels
Project description:The DSB-machinery, which induces the programmed DNA double-strand breaks (DSBs) in leptotene and zygotene stages during meiosis, needs to be kept in silence after the initiation of pachytene stage to prevent the activation of DSB checkpoint that may lead to meiotic arrest or apoptosis of germ cells. However, the mechanisms underlying this repression remain largely unknown. Here, we report that ZFP541, a germ cell-specific zinc finger protein, is responsible for the suppression of DSBs formation at late pachytene. Lack of Zfp541 in mice leads to generation of DSBs in late pachytene spermatocytes by DSB formation related-proteins and causes male infertility due to meiotic failure. Plated-based scRNA-seq of Zfp541-/- spermatocytes revealed that ZFP541 negatively regulates many meiotic prophase genes, including genes for DSB formation and their upstream transcriptional regulators, in late pachytene spermatocytes. These results were confirmed by 10x single-cell RNA-seq data on spermatogenesis of Zfp541-/- testes, which suggested that Zfp541 is required for repressing the activation of pre-pachytene gene expression programs from early to late pachytene. ZFP541 ChIP-seq on pachytene and diplotene spermatocytes demonstrated that ZFP541 occupies the promoters of meiosis initiators (e.g., Meiosin and Rxra) and a subset of their downstream genes to repress their transcription, and thus prevent the reactivation of pre-pachytene gene expression programs in pachytene spermatocytes. Thus, our results not only revealed the role of ZFP541 in maintaining the repression of pre-pachytene transcriptional programs in pachytene spermatocytes but also provide new insight into the regulation of meiotic progression by timely turning off pre-pachytene genes.
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Project description:Faithful gamete formation during meiosis requires that kinetochores take on new functions that impact homolog pairing/recombination and their attachments to microtubules. We used a proteomics pipeline to determine the global composition of centromeric chromatin and kinetochores at distinct meiotic stages. Our datasets uncover an unanticipated role for the Ctf19CCAN inner kinetochore sub-complex in gametogenesis. We show that components of the Ctf19 complex that are dispensable for mitotic growth become critical for assembly of a functional kinetochore upon meiotic entry. Consequently, in the absence of these factors, chromosomes fail to attach to meiotic spindles and produce inviable gametes due to gross segregation errors. Our evidence suggests that functional kinetochore assembly is driven by Ctf19CCAN complex-dependent Ipl1AURORA B positioning at the inner kinetochore. Thus, our global view of kinetochore composition in meiosis reveals the extent of kinetochore remodelling during gametogenesis and uncovers a kinetochore assembly pathway that becomes critical in meiosis.
2021-02-23 | PXD019754 | Pride
Project description:Meiosis was compared in rad50-1 and wild type strains of C. cinerea at 6 time points spanning the meiotic timecourse. Abstract: The basidiomycete Coprinopsis cinerea is well-suited to studies of meiosis because meiosis progresses synchronously in ten million cells within each mushroom cap. Approximately 20% of C. cinerea genes exhibit changing expression during meiosis, but meiosis and mushroom development happen concurrently so differentially expressed genes might not be directly involved in meiotic processes. Using microarrays, we examined global gene expression across a meiotic time course in two mutants in which meiosis arrests but mushrooms develop normally. Genes differentially expressed in the mutants compared to wild type are likely to be involved in meiosis and sporulation as opposed to mushroom development. In rad50-1, which arrests in late prophase, RNA abundance for a group of early meiotic genes remains high, while the expression of a group of late meiotic genes is never induced. In contrast, in msh5-22 (which fails to undergo pre-meiotic DNA replication), both early and late meiotic genes are underexpressed relative to wild type at late meiotic time points as the cells die. Genes that are differentially expressed in both mutants are particularly strong candidates for playing roles in meiosis and sporulation.
2012-05-15 | GSE37942 | GEO
Project description:Meiosis was compared in msh5-22 and wild type strains of C. cinerea at 6 time points spanning the meiotic timecourse. Abstract: The basidiomycete Coprinopsis cinerea is well-suited to studies of meiosis because meiosis progresses synchronously in ten million cells within each mushroom cap. Approximately 20% of C. cinerea genes exhibit changing expression during meiosis, but meiosis and mushroom development happen concurrently so differentially expressed genes might not be directly involved in meiotic processes. Using microarrays, we examined global gene expression across a meiotic time course in two mutants in which meiosis arrests but mushrooms develop normally. Genes differentially expressed in the mutants compared to wild type are likely to be involved in meiosis and sporulation as opposed to mushroom development. In rad50-1, which arrests in late prophase, RNA abundance for a group of early meiotic genes remains high, while the expression of a group of late meiotic genes is never induced. In contrast, in msh5-22 (which fails to undergo pre-meiotic DNA replication), both early and late meiotic genes are underexpressed relative to wild type at late meiotic time points as the cells die. Genes that are differentially expressed in both mutants are particularly strong candidates for playing roles in meiosis and sporulation.
2012-05-15 | GSE37943 | GEO