Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Meiosis-specific ZFP541 repressor complex promotes developmental progression of meiotic prophase towards completion during mouse spermatogenesis.

ABSTRACT: During spermatogenesis, meiosis is accompanied by a robust alteration in gene expression and chromatin status. However, it remains elusive how the meiotic transcriptional program is established to ensure completion of meiotic prophase. Here, we identify a protein complex that consists of germ-cell-specific zinc-finger protein ZFP541 and its interactor KCTD19 as the key transcriptional regulators in mouse meiotic prophase progression. Our genetic study shows that ZFP541 and KCTD19 are co-expressed from pachytene onward and play an essential role in the completion of the meiotic prophase program in the testis. Furthermore, our ChIP-seq and transcriptome analyses identify that ZFP541 binds to and suppresses a broad range of genes whose function is associated with biological processes of transcriptional regulation and covalent chromatin modification. The present study demonstrates that a germ-cell specific complex that contains ZFP541 and KCTD19 promotes the progression of meiotic prophase towards completion in male mice, and triggers the reconstruction of the transcriptional network and chromatin organization leading to post-meiotic development.

SUBMITTER: Horisawa-Takada Y

PROVIDER: S-EPMC8169937 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

p53 Controls Meiotic Prophase Progression and Crossover Formation.

Project description:Meiosis initiates with the formation of double strand breaks (DSBs) throughout the genome. To avoid genomic instability, these DSBs need to be correctly repaired by homologous recombination. Surveillance mechanisms involving the DNA damage response (DDR) pathway ATM-CHK2-p53 can detect the persistence of unrepaired DBSs and activate the recombination-dependent arrest at the pachytene stage. However, a complete understanding of p53 functions under normal physiological conditions remains lacking. Here, we report a detailed analysis of the p53 role during meiotic prophase in mice spermatocytes. We show that the absence of p53 regulates prophase progression by slowing down the pachytene stage when the recombination-dependent arrest occurs. Furthermore, our results show that p53 is necessary for proper crossover (CO) formation and localization. Our study contributes to a deeper understanding of p53 roles during the meiotic prophase.

| S-EPMC9456223 | biostudies-literature

Meiotic cohesin promotes pairing of nonhomologous centromeres in early meiotic prophase.

Project description:A period of pairing between nonhomologous centromeres occurs early in meiosis in a diverse collection of organisms. This early, homology-independent, centromere pairing, referred to as centromere coupling in budding yeast, gives way to an alignment of homologous centromeres as homologues synapse later in meiotic prophase. The regulation of centromere coupling and its underlying mechanism have not been elucidated. In budding yeast, the protein Zip1p is a major component of the central element of the synaptonemal complex in pachytene of meiosis, and earlier, is essential for centromere coupling. The experiments reported here demonstrate that centromere coupling is mechanistically distinct from synaptonemal complex assembly. Zip2p, Zip3p, and Red1p are all required for the assembly of Zip1 into the synaptonemal complex but are dispensable for centromere coupling. However, the meiotic cohesin Rec8p is required for centromere coupling. Loading of meiotic cohesins to centromeres and cohesin-associated regions is required for the association of Zip1 with these sites, and the association of Zip1 with the centromeres then promotes coupling. These findings reveal a mechanism that promotes associations between centromeres before the assembly of the synaptonemal complex, and they demonstrate that chromosomes are preloaded with Zip1p in a manner that may promote synapsis.

| S-EPMC2877639 | biostudies-literature

Zscan4 is expressed specifically during late meiotic prophase in both spermatogenesis and oogenesis.

Project description:Mouse zinc finger and SCAN domain containing 4 (Zscan4) proteins, which are encoded by multiple copies of Zscan4 genes, are expressed specifically in preimplantation embryos in vivo and embryonic stem (ES) cells in vitro. However, the expression patterns of mouse Zscan4 in vivo have been largely elusive. Here, we show that Zscan4 proteins are expressed in adult ovaries and testes. In ovaries, Zscan4 proteins were detected in germinal vesicle (GV) stage oocytes in antral follicles, indicating that Zscan4 genes are activated during the diplotene/dictyate stage in meiotic prophase I. Remarkably, Zscan4 showed different spatial localization patterns between two distinct GV oocytes, which can be distinguished by global chromatin organization-surrounded nucleolus (SN) and non-surrounded nucleolus (NSN). These spatiotemporal differences in Zscan4 localizations correlated with the transition of RNA polymerase II-mediated transcriptional status during GV oocyte maturation. In testes, Zscan4 proteins were detected in spermatocytes at late pachytene/diplotene stages and in Sertoli cells. These results suggest that Zscan4 may play critical roles during late meiotic prophase in both males and females.

| S-EPMC5311088 | biostudies-literature

Functional dynamics of H3K9 methylation during meiotic prophase progression.

Project description:Histone H3 lysine 9 (H3K9) methylation is a crucial epigenetic mark of heterochromatin formation and transcriptional silencing. G9a is a major mammalian H3K9 methyltransferase at euchromatin and is essential for mouse embryogenesis. Here we describe the roles of G9a in germ cell development. Mutant mice in which G9a is specifically inactivated in the germ-lineage displayed sterility due to a drastic loss of mature gametes. G9a-deficient germ cells exhibited perturbation of synchronous synapsis in meiotic prophase. Importantly, mono- and di-methylation of H3K9 (H3K9me1 and 2) in G9a-deficient germ cells were significantly reduced and G9a-regulated genes were overexpressed during meiosis, suggesting that G9a-mediated epigenetic gene silencing is crucial for proper meiotic prophase progression. Finally, we show that H3K9me1 and 2 are dynamically and sex-differentially regulated during the meiotic prophase. This genetic and biochemical evidence strongly suggests that a specific set of H3K9 methyltransferase(s) and demethylase(s) coordinately regulate gametogenesis.

| S-EPMC1933398 | biostudies-literature

FBXW24 controls female meiotic prophase progression by regulating SYCP3 ubiquitination.

Project description:BackgroundAn impeccable female meiotic prophase is critical for producing a high-quality oocyte and, ultimately, a healthy newborn. SYCP3 is a key component of the synaptonemal complex regulating meiotic homologous recombination. However, what regulates SYCP3 stability is unknown.MethodsFertility assays, follicle counting, meiotic prophase stage (leptotene, zygotene, pachytene and diplotene) analysis and live imaging were employed to examine how FBXW24 knockout (KO) affect female fertility, follicle reserve, oocyte quality, meiotic prophase progression of female germ cells, and meiosis of oocytes. Western blot and immunostaining were used to examined the levels & signals (intensity, foci) of SYCP3 and multiple key DSB indicators & repair proteins (γH2AX, RPA2, p-CHK2, RAD51, MLH1, HORMAD1, TRIP13) after FBXW24 KO. Co-IP and immuno-EM were used to examined the interaction between FBXW24 and SYCP3; Mass spec was used to characterize the ubiquitination sites in SYCP3; In vivo & in vitro ubiquitination assays were utilized to determine the key sites in SYCP3 & FBXW24 for ubiquitination.ResultsFbxw24-knockout (KO) female mice were infertile due to massive oocyte death upon meiosis entry. Fbxw24-KO oocytes were defective due to elevated DNA double-strand breaks (DSBs) and inseparable homologous chromosomes. Fbxw24-KO germ cells showed increased SYCP3 levels, delayed prophase progression, increased DSBs, and decreased crossover foci. Next, we found that FBXW24 directly binds and ubiquitinates SYCP3 to regulate its stability. In addition, several key residues important for SYCP3 ubiquitination and FBXW24 ubiquitinating activity were characterized.ConclusionsWe proposed that FBXW24 regulates the timely degradation of SYCP3 to ensure normal crossover and DSB repair during pachytene. FBXW24-KO delayed SYCP3 degradation and DSB repair from pachytene until metaphase II (MII), ultimately causing failure in oocyte maturation, oocyte death, and infertility.

| S-EPMC9299759 | biostudies-literature

Implementation of meiosis prophase I programme requires a conserved retinoid-independent stabilizer of meiotic transcripts.

Project description:Sexual reproduction is crucially dependent on meiosis, a conserved, specialized cell division programme that is essential for the production of haploid gametes. Here we demonstrate that fertility and the implementation of the meiotic programme require a previously uncharacterized meiosis-specific protein, MEIOC. Meioc invalidation in mice induces early and pleiotropic meiotic defects in males and females. MEIOC prevents meiotic transcript degradation and interacts with an RNA helicase that binds numerous meiotic mRNAs. Our results indicate that proper engagement into meiosis necessitates the specific stabilization of meiotic transcripts, a previously little-appreciated feature in mammals. Remarkably, the upregulation of MEIOC at the onset of meiosis does not require retinoic acid and STRA8 signalling. Thus, we propose that the complete induction of the meiotic programme requires both retinoic acid-dependent and -independent mechanisms. The latter process involving post-transcriptional regulation likely represents an ancestral mechanism, given that MEIOC homologues are conserved throughout multicellular animals.

| S-EPMC4729902 | biostudies-literature

The telomere bouquet facilitates meiotic prophase progression and exit in fission yeast.

Project description:During meiotic prophase, chromosome arrangement and oscillation promote the pairing of homologous chromosomes for meiotic recombination. This dramatic movement involves clustering of telomeres at the nuclear membrane to form the so-called telomere bouquet. In fission yeast, the telomere bouquet is formed near the spindle pole body (SPB), which is the microtubule organising centre, functionally equivalent to the metazoan centrosome. Disruption of bouquet configuration impedes homologous chromosome pairing, meiotic recombination and spindle formation. Here, we demonstrate that the bouquet is maintained throughout meiotic prophase and promotes timely prophase exit in fission yeast. Persistent DNA damages, induced during meiotic recombination, activate the Rad3 and Chk1 DNA damage checkpoint kinases and extend the bouquet stage beyond the chromosome oscillation period. The auxin-inducible degron system demonstrated that premature termination of the bouquet stage leads to severe extension of prophase and consequently spindle formation defects. However, this delayed exit from meiotic prophase was not caused by residual DNA damage. Rather, loss of chromosome contact with the SPB caused delayed accumulation of CDK1-cyclin B at the SPB, which correlated with impaired SPB separation. In the absence of the bouquet, CDK1-cyclin B localised near the telomeres but not at the SPB at the later stage of meiotic prophase. Thus, bouquet configuration is maintained throughout meiotic prophase, by which this spatial organisation may facilitate local and timely activation of CDK1 near the SPB. Our findings illustrate that chromosome contact with the nuclear membrane synchronises meiotic progression of the nucleoplasmic chromosomes with that of the cytoplasmic SPB.

| S-EPMC5674143 | biostudies-literature

Reduced meiotic crossovers and delayed prophase I progression in AtMLH3-deficient Arabidopsis.

Project description:Characterization of AtMLH3, the Arabidopsis homologue of the prokaryotic MutL mismatch repair gene, reveals that it is expressed in reproductive tissue where it is required for normal levels of meiotic crossovers (COs). Immunocytological studies in an Atmlh3 mutant indicate that chromosome pairing and synapsis proceed with normal distribution of the early recombination pathway proteins. Localization of the MutS homologue AtMSH4 occurs, suggesting that double Holliday junctions (dHjs) are formed, but the MutL homologue AtMLH1, which forms a heterocomplex with AtMLH3, fails to localize normally. Loss of AtMLH3 results in an approximately 60% reduction in COs and is accompanied by a substantial delay of approximately 25 h in prophase I progression. Analysis of the chiasma distribution in Atmlh3 suggests that dHj resolution can occur, but in contrast to wild type where most or all dHjs are directed to form COs the outcome is biased in favour of a non-CO outcome by a ratio of around 2 to 1. The data are compatible with a model whereby the MutL complex imposes a dHj conformation that ensures CO formation.

| S-EPMC1422170 | biostudies-literature

t-SNARE Syntaxin2 (STX2) is implicated in intracellular transport of sulfoglycolipids during meiotic prophase in mouse spermatogenesis.

Project description:Syntaxin2 (STX2), also known as epimorphin, is a member of the SNARE family of proteins, with expression in various types of cells. We previously identified an ENU-induced mutation, repro34, in the mouse Stx2 gene. The Stx2(repro34) mutation causes male-restricted infertility due to syncytial multinucleation of spermatogenic cells during meiotic prophase. A similar phenotype is also observed in mice with targeted inactivation of Stx2, as well as in mice lacking enzymes involved in sulfoglycolipid synthesis. Herein we analyzed expression and subcellular localization of STX2 and sulfoglycolipids in spermatogenesis. The STX2 protein localizes to the cytoplasm of germ cells at the late pachytene stage. It is found in a distinct subcellular pattern, presumably in the Golgi apparatus of pachytene/diplotene spermatocytes. Sulfoglycolipids are produced in the Golgi apparatus and transported to the plasma membrane. In Stx2(repro34) mutants, sulfoglycolipids are aberrantly localized in both pachytene/diplotene spermatocytes and in multinucleated germ cells. These results suggest that STX2 plays roles in transport and/or subcellular distribution of sulfoglycolipids. STX2 function in the Golgi apparatus and sulfoglycolipids may be essential for maintenance of the constriction between neighboring developing spermatocytes, which ensures ultimate individualization of germ cells in later stages of spermatogenesis.

| S-EPMC6322434 | biostudies-literature

RNA polymerase II pausing is essential during spermatogenesis for appropriate gene expression and completion of meiosis.

Project description:Male germ cell development requires precise regulation of gene activity in a cell-type and stage-specific manner, with perturbations in gene expression during spermatogenesis associated with infertility. Here, we use steady-state, nascent and single-cell RNA sequencing strategies to comprehensively characterize gene expression across male germ cell populations, to dissect the mechanisms of gene control and provide new insights towards therapy. We discover a requirement for pausing of RNA Polymerase II (Pol II) at the earliest stages of sperm differentiation to establish the landscape of gene activity across development. Accordingly, genetic knockout of the Pol II pause-inducing factor NELF in immature germ cells blocks differentiation to spermatids. Further, we uncover unanticipated roles for Pol II pausing in the regulation of meiosis during spermatogenesis, with the presence of paused Pol II associated with double-strand break (DSB) formation, and disruption of meiotic gene expression and DSB repair in germ cells lacking NELF.

| S-EPMC10824759 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data