MAX controls meiotic entry in sexually undifferentiated germ cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE244318 | GEO | 2024/09/29
REPOSITORIES: GEO
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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:MAX controls meiotic entry in sexually undifferentiated germ cells
| PRJNA1022400 | ENA
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:We explored Max ablation-mediated up-regulation of germ-related genes, especially meiosis-related genes in mouse embryonic stem cells which were cultured either under conventional mouse ES medium or 2i condition using inhibitors against MEK and GSK3b.
2016-03-31 | GSE65700 | GEO
Project description:We explored Max ablation-mediated up-regulation of germ-related genes, especially meiosis-related genes in mouse embryonic stem cells which were cultured either under conventional mouse ES medium or 2i condition using inhibitors against MEK and GSK3b. Effect of culture conditions (conventional mouse ES medium or 2i condition) on the expression profile of germ-related genes in Max expression ablated ES cells were examined using inducible Max-null ES cells in which Max gene had been homozygously disrupted, but carries Max cDNA in ROSA26 locus with tetracycline-off system.
2016-03-31 | E-GEOD-65700 | biostudies-arrayexpress
Project description:Ablation of Max expression induces meiotic onset in sexually undifferentiated germ cells
| PRJNA976654 | ENA
Project description:The switch from mitosis to meiosis is a major transition that takes place during germ cell development. The precise sequence and the different gene expression programs activated during this process are only partly known. Here, we applied single-cell mRNA sequencing to interrogate the transcriptional changes that occur during the early steps of male germ cell differentiation. We isolated single cells from testes using a Dazl-GFP reporter mouse, which allowed us to focus on germ cells undergoing the mitotic to meiotic transition. We identified 4 distinct meiotic stages with unique transcriptome profiles and reconstructed the timeline of the meiotic entry in silico, from spermatogonia up to the pachytene stage, identifying transcriptional changes with an unprecedented resolution. This allowed us to characterize 3 major transitions in the meiotic prophase 1 of the male germline: meiotic entry, the meiotic sex chromosome inactivation (MSCI), and concomitant pachytene transcriptional activation. Meiotic entry is initiated following the downregulation of a tightly connected set of pluripotency factors and accompanied by a global transcriptional silencing. In contrast, during subsequent sex chromosome inactivation at the zygotene stage, gene silencing proceeds in a defined order, related to gene function.
2021-05-22 | GSE114788 | GEO
Project description:Male germ cells establish a unique heterochromatin domain, the XY-body, early in meiosis. How this domain is maintained through the end of meiosis and into post-meiotic germ cell differentiation is poorly understood. ADAD2 is a late meiotic male germ cell specific RNA binding protein, loss of which leads to post-meiotic germ cell defects. Analysis of ribosome association in Adad2 mutants revealed defective translation of Mdc1, a key regulator of XY-body formation, late in meiosis. As a result, Adad2 mutants show normal establishment but failed maintenance of the XY-body. Observed XY-body defects are concurrent with abnormal autosomal heterochromatin and ultimately lead to severely perturbed post-meiotic germ cell heterochromatin and cell death. These findings highlight the requirement of ADAD2 for Mdc1 translation, the role of MDC1 in maintaining meiotic male germ cell heterochromatin, and the importance of late meiotic heterochromatin for normal post-meiotic germ cell differentiation.
2021-12-11 | GSE190525 | GEO
Project description:In embryonic stem cells (ESCs), the expression of development-related genes, including germ cell-related genes, is globally repressed. The transcription factor MAX represses germ cell-related gene expression in ESCs via PCGF6-polycomb repressive complex (PRC)1, which consists of several epigenetic factors. However, we predicted that MAX represses germ cell-related gene expression through several additional mechanisms because PCGF6-PRC1 regulates the expression of only a subset of genes repressed by MAX. Here, we report that MAX associated with DNA methyltransferases (DNMTs) and the histone methyltransferase SETDB1 cooperatively control germ cell-related gene expression in ESCs. Both DNA methylation and histone H3 lysine 9 tri-methylation of the promoter regions of several germ cell-related genes were not affected by knockout of the PRC1 components, indicating that the MAX-DNMT and MAX-SETDB1 pathways are independent of the PCGF6-PRC1 pathway. Our findings provide insights into our understanding of MAX-based repressive mechanisms of germ cell-related genes in ESCs.
2018-08-31 | GSE102610 | GEO
Project description:Meiosis occurs specifically in germ cells to produce sperm and oocytes that are competent for sexual reproduction. Multiple factors are required for successful meiotic entry, progression, and termination. Trimethylation of histone H3 on lysine 4 (H3K4me3), a mark of active transcription, has been implicated in spermatogenesis by forming double strand breaks (DSBs). The role of H3K4me in transcriptional regulation during meiosis however, remains poorly understood. Here, we reveal that mouse CXXC finger protein 1 (Cfp1), a component of H3K4me methyltransferases Setd1a/b, is dynamically expressed in differentiating male germ cells and safeguards meiosis by controlling gene expression. Depletion of Cfp1 in male germ cells resulted in infertility with reduced H3K4me3, spermatogenic arrest, and repression of essential germ cell development and meiosis genes. Importantly, ChIP-Seq analysis revealed that Cfp1 is mainly enriched at transcriptional start sites to promote gene expression and H3K4me2/3 levels at pachytene stage. The most highly enriched genes were associated with meiosis and homologous recombination during differentiation of spermatocytes to round spermatids. Additionally, missense mutations of human CFP1 were prevalent in patients with nonobstructive azoospermia. Therefore, our study establishes a mechanistic link between CFP1-mediated transcriptional control and meiotic progression, and provides unprecedented genetic basis for understanding human sterility.
2018-10-10 | GSE120994 | GEO