Ablation of Max expression induces meiotic onset in sexually undifferentiated germ cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA976654 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:MAX controls meiotic entry in sexually undifferentiated germ cells
| PRJNA1022400 | ENA
Project description:MAX (MYC Associated Factor X) is generally known as a mandatory partner for MYC transcription factor, which activates various genes involved in cell growth and metabolism. On the other hand, MAX, when interacting with MGA, forms the polycomb repressive complex (PRC) 1.6, one of the subtypes of PRC1, which directs the transcriptionally repressed chromatin state. Although physiological significance is not known at present, we have previously demonstrated that mouse embryonic stem cells (ESCs) bear a potential to onset meiosis, albeit not germ cells, and PRC1.6 prevent ESCs from their ectopic onset of meiosis (Suzuki et al., 2016, Nat. Commun. 7:11056 doi: 10.1038/ncomms11056). In this study, we aimed to investigate the role of Max in germ cells in vivo by performing the primordial germ cell-specific knockout of the Max gene.
2024-03-13 | GSE233556 | GEO
Project description:In mammals, female, but not male, germ cells onset meiosis physiologically during embryonic stages. We examined whether germ cell-specific disruption of Max gene leads to the activation of meiosis-related genes in embryonic male germ cells by single cell RNA sequencing.
2024-09-29 | GSE244318 | GEO
Project description:Meiosis is a specialized type of cell division that occurs physiologically only in germ cells. We previously demonstrated that MYC-associated factor X (MAX) blocks the ectopic onset of meiosis in embryonic and germline stem cells in culture systems. Here, we investigated the Max gene's role in mouse primordial germ cells. Although Max is generally ubiquitously expressed, we revealed that sexually undifferentiated male and female germ cells had abundant MAX protein because of their higher Max gene expression than somatic cells. Moreover, our data revealed that this high MAX protein level in female germ cells declined significantly around physiological meiotic onset. Max disruption in sexually undifferentiated germ cells led to ectopic and precocious expression of meiosis-related genes, including Meiosin, the gatekeeper of meiotic onset, in both male and female germ cells. However, Max-null male and female germ cells did not complete the entire meiotic process, but stalled during its early stages and were eventually eliminated by apoptosis. Additionally, our meta-analyses identified a regulatory region that supports the high Max expression in sexually undifferentiated male and female germ cells. These results indicate the strong connection between the Max gene and physiological onset of meiosis in vivo through dynamic alteration of its expression.
| S-EPMC10909893 | biostudies-literature
Project description:Meiosis is a key step during germ cell differentiation, accompanied by the activation of thousands of genes through germline-specific chromatin reorganization. The chromatin remodeling mechanisms underpinning early meiotic stages remain poorly understood. Here we focus on the function of one of the major autism genes, CHD8, in spermatogenesis, based on the epidemiological association between autism and low fertility rates. Specific ablation of Chd8 in germ cells results in gradual depletion of undifferentiated spermatogonia as well as failure of meiotic double strand formation followed by arrest at meiotic prophase I and cell death. Transcriptional analyses demonstrate that CHD8 is required for extensive activation of spermatogenic genes in spermatogonia, necessary for spermatogonial proliferation and meiosis. CHD8 directly binds to promoters of genes crucial for meiosis, including H3K4me3 histone methyltransferase genes, meiotic cohesin genes, HORMA domain containing genes, synaptonemal complex genes, and DNA damage response genes. Through transcriptionally regulating the interaction of these meiosis-related genes, we argue that CHD8 contributes to meiotic double strand break formation and subsequent meiotic progression. Our study uncovers an essential role of CHD8 for the proliferation of undifferentiated spermatogonia and the successful progression of meiotic prophase I.
2023-12-31 | GSE252121 | GEO
Project description:The aim of this study was to study the gene expression profile in developing female and male gonads of Xenopus laevis at four stages: at the Nieuwkoop-Faber stage 50 (genital ridge), at NF53 (sex-determining period), NF56 (the onset of sexual differentiation), NF62 (gonads sexually differentiated).
2017-10-18 | GSE105103 | GEO
Project description:Meiosis is a highly complex process that underpins recombination in sexually reproducing organisms. Recent genomics studies suggest that up to several thousand genes/proteins contribute to the meiotic pathway, yet relatively few have been functionally characterised. Our understanding of the physical interactions between meiotic proteins and how the meiotic machinery interacts with other components of the cell is also limited. In this study, we used affinity proteomics targeting the meiotic chromosome axis protein, ASY1, to enrich for axis-associated proteins in Brassica oleracea anthers or meiocytes in prophase I of meiosis. LC-MS/MS analysis identified 540 proteins which co-immunoprecipitated with ASY1 in a sample-specific manner. These correspond to 485 Arabidopsis orthologues, 90% of which form a coherent predicted protein-protein interaction network which includes known and novel meiotic proteins, based on mutant analysis, but also proteins more usually associated with other cellular processes including replication and proteolysis. Our data provided new insights into the role of the chromosome axis in plant meiosis. We identified a novel axis-associated protein and showed that during prophase I, ASY1 and its interacting partner, ASY3, are extensively phosphorylated. Further studies targeting other meiotic proteins may ultimately enable the construction of a comprehensive meiosis protein-protein interaction network for higher plants.
2017-11-01 | PXD006042 | Pride
Project description:The maintenance of spermatogenesis in adult males is dependent on a population of mitotic germ cells with self-renewal potential known as undifferentiated spermatogonia. Regulation of undifferentiated spermatogonia function is dependent on transcriptional and post-transcriptional mechanisms. We have identified an essential role for the RNA helicase DDX5 in undifferentiated spermatogonia through generation of a UBC-CreERT2;Ddx5flox/flox mouse model that allows tamoxifen-dependent Ddx5 ablation. To identify genes regulated by DDX5, we generated lines of cultured undifferentiated spermatogonia from these mice and treated cells with tamoxifen (TMX) to induce Ddx5 knockout or vehicle (VEH) as a control, and performed RNA-sequencing analysis to compare these conditions.
2019-04-02 | GSE127275 | 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.
This model is hosted on BioModels Database
and identified
by: BIOMD0000000626
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000626 | BioModels
Project description:Meiotic synapsis and recombination ensure correct homologous segregation and genetic diversity. Asynapsed homologues are transcriptionally inactivated by meiotic silencing, which serves a surveillance function and in males drives meiotic sex chromosome inactivation. Silencing depends on the DNA damage response (DDR) network, but how DDR proteins engage repressive chromatin marks is unknown. We identify the histone H3-lysine-9 methyltransferase SETDB1 as the bridge linking the DDR to silencing in male mice. At the onset of silencing, X-chromosome H3K9 trimethylation (H3K9me3) enrichment is downstream of DDR factors. Without Setdb1, the X chromosome accrues DDR proteins but not H3K9me3. Consequently, sex chromosome remodelling and silencing fails, causing germ cell apoptosis. Our data implicate TRIM28 in linking the DDR to SETDB1, and uncover additional factors with putative meiotic XY-silencing functions. Furthermore, we show that SETDB1 imposes timely expression of meiotic and post-meiotic genes. Setdb1 thus unites the DDR network, asynapsis and meiotic chromosome silencing.
2018-11-01 | GSE107671 | GEO