CFP1 safeguards male meiotic progression by regulating meiotic gene expression [array]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE121240 | GEO | 2018/10/16
REPOSITORIES: GEO
Similar Datasets
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
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. Among them, trimethylation of histone H3 on lysine 4 (H3K4me3), a mark of active transcription, has been implicated in spermatogenesis by forming double-strand breaks (DSBs). However, the role of H3K4me in transcriptional regulation during meiosis remains poorly understood. Here, we reveal that mouse CXXC finger protein 1 (Cfp1), a component of the H3K4 methyltransferase Setd1a/b, is dynamically expressed in differentiating male germ cells and safeguards meiosis by controlling gene expression. Genetic ablation of mouse CFP1 in male germ cells caused complete infertility with failure in prophase I of the 1st meiosis. Mechanistically, CFP1 binds to genes essential for spermatogenesis, and its loss leads to a reduction in H3K4me3 levels and gene expression. Importantly, CFP1 is highly enriched within the promoter/TSS of target genes to elevate H3K4me3 levels and gene expression at the pachytene stage of meiotic prophase I. The most enriched genes were associated with meiosis and homologous recombination during the differentiation of spermatocytes to round spermatids. Therefore, our study establishes a mechanistic link between CFP1-mediated transcriptional control and meiotic progression and might provide an unprecedented genetic basis for understanding human sterility.
| S-EPMC9440128 | biostudies-literature
Project description:CFP1 safeguards male meiotic progression by regulating meiotic gene expression
| PRJNA495328 | ENA
Project description:CFP1 safeguards male meiotic progression by regulating meiotic gene expression [array]
| PRJNA496430 | ENA
Project description:Nitrogen starvation drives meiosis in yeasts1, while retinoic acid (RA) is required for mammalian meiosis through the activation of its germline-specific target, stimulated by retinoic acid gene 8 (Stra8).Here, by using single-cell transcriptome analysis of wild-type and Stra8-deficient testes, our data revealed that the expression of major metabolic genes are downregulated during germ cell entry into meiosis. Recently, we collected mouse testicular cells from wild-type and Stra8-deficient mice at postnatal day 12 (P12) and P21 for single cell RNA-sequencing (scRNA-seq). Upon scRNA-seq, we obtained a total of 23,470 cells from these samples. Using stringent quality control, 22,839 cells were selected for further analysis. All cells, including both wild-type and Stra8-deficient testicular cells, were pooled together to perform clustering analysis, which revealed 6 major cell clusters based on their distinct gene expression patterns. We annotated these six clusters by using known marker genes, including spermatogonia (SPG; Stra8; 3,941 cells), spermatocyte (SPC; Syce1; 4,924 cells), spermatid (STD; Acrv1; 710 cells), Sertoli cell (SC; Sox9; 9,488 cells), Myeloid (MYD; Acta2; 3,531 cells), and Leydig Cells (LY; Star; 245 cells). There is an increase in the percentage of spermatogonia in Stra8-deficient testes at both P12 (28% versus 14% in wild-type) and P21 (17% versus 10% in wild-type). At P21, while spermatocytes are abundant and spermatid are formed in wild-type testes, there are only a few spermatocytes (0.2% versus 73% in wild-type), and spermatids are absent in Stra8-deficient testes. Signature genes are enriched for GO terms for distinct biological function and metabolic pathways in different cell types.
2023-10-03 | GSE211390 | GEO
Project description:Characterization of the molecular changes occurring at murine meiotic initiation: identification of gene expression changes in male germ cells undergoing meiotic initiation; identification of STRA8-bound sites in mouse testes enriched for germ cells initiating meiosis
2019-02-26 | GSE115928 | GEO
Project description:Spermatogenesis is a complex process involving meiosis in spermatocytes and dynamic epigenetic changes that ensure the inheritance of genetic traits. CXXC finger protein 1 (Cfp1), a component of the SETD1 methyltransferase complex, has a binding domain specific for unmethylated CpG sites. Previous studies have implicated Cfp1 in the epigenetic changes required for meiosis in spermatocytes, and its loss of function has been shown to result in male sterility. In this study, we aimed to gain a comprehensive understanding of Cfp1 function in spermatocytes by examining its genome-wide binding profile and the resulting changes in DNA methylation and H3K4me3, a histone modification associated with active gene transcription. We isolated Cfp1-depleted spermatocytes and performed H3K4me3 ChIP-seq and reduced-representation bisulfite sequencing (RRBS) analyses. By integrating these multi-omics datasets with Cfp1 ChIP-seq analysis, we identified genes directly regulated by Cfp1 and characterised the epigenetic changes associated with its regulation. Our analysis shows that Cfp1 not only directly affects the regulation of genes essential for meiosis, but also has a significant impact on the overall regulation of gene expression. The knowledge gained from studying the regulatory mechanisms of Cfp1 in spermatocytes provides valuable information about the reproductive process and contributes to our understanding of the underlying causes of infertility.
2023-08-10 | GSE240280 | GEO
Project description:Purpose: This transcriptomic analysis aims at unveiling all possible genes orchestrated by Cfp1, which is evidently required for insect pathogenicity and virulence-related cellular events of Metarhizium robertsii. Methods: Total RNAs were extracted from three 3-day-old hyphal cultures (replicates) of cfp1 disruption and wild-type strains grown under normal culture conditionsand and subjected to deep sequencing on Illumina NovaseqTM 6000 platform. The sequence reads that passed quality filters were mapped to the genome of Metarhizium robertsii. All genes differentially expressed in the disruptant versus the wild-type strain were enriched to GO function classes and KEGG pathways. Results: The resultant transcriptome comprises 10681 detected genes. Among those, 605 genes were dysregulated in the absence of cfp1, including 356 down-regulated and 249 up-regulated. Conclusions: Cfp1 lacking any predictable function domain has profound impact on the genomic expression of Metarhizium robertsii.
2022-02-26 | GSE197269 | GEO
Project description:Spermiogenesis defines the final phase of male germ cell differentiation. Multiple deubiquitinating enzymes have been linked to spermiogenesis, yet the impacts of deubiquitination on spermiogenesis remain poorly characterized. Here, we investigated the function of UAF1 in mouse spermiogenesis and male fertility. We selectively deleted Uaf1 in premeiotic germ cells using Stra8-Cre knock-in mouse strain (Uaf1 sKO), and found that Uaf1 is essential for spermiogenesis and male fertility. We found that UAF1 interacts and colocalizes with USP1 in testes. Conditional knockout of Uaf1 in testes results in disturbed expression and localization of USP1, suggesting that UAF1 regulates spermiogenesis through the function of the deubiquitinating enzyme USP1. We used tandem mass tag-based proteomics to identify differentially expressed proteins and potential underlying mechanisms, and found that conditional knockout Uaf1 in testes results in reduced levels of proteins essential for spermiogenesis. Thus, the UAF1/USP1 deubiquitinase complex is essential for normal spermiogenesis by regulating the levels of spermiogenesis-related proteins.
2024-02-07 | PXD046120 | Pride
Project description:Through RNA-seq of wildtype and CFP1-deleted GV oocytes of different ages, zygotes and 2-cell embryos and whole genome bisulfite sequencing of GV oocytes, We show here that CFP1 is responsible for epigenetic maturation in oocytes. Deletion of CFP1 directly decreased histone H3K4 trimethylation and caused global down-regulation of gene expression in oocytes.These genes are involved in cytoplasmic lattice formation, maternal-zygotic transition and epigenetic maturation. Maternal CFP1-deleted oocytes had fewer CPLs in the cytoplasm and the organelles were severely aggregated, which further caused defects in α-tubulin polymerization and aneuploidy in meiosis II. The genome was less methylated and methylation of maternal DNA was impaired after CFP1 deletion. Therefore CFP1-deleted oocytes fail to complete epigenetic maturation as well as cytoplasmic maturation and nuclear maturation and unable to gain developmental competence during oogenesis.
2017-09-30 | GSE85019 | GEO