Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CxxC Finger Protein 1-mediated Histone H3 Lysine-4 Trimethylation is Essential for Proper Meiotic Crossover Formation in Mice

ABSTRACT: CXXC finger protein 1 (Cfp1) is a DNA-binding component of the SETD1 methyltransferase complex, targets SETD1A/B to most CpG islands (CpGI), and mediates the generation of H3K4me3. Deficiency of CFP1 in mice leads to pre-implantation lethality. Previous data suggest an indispensable role of CFP1 in germ cell development and meiosis. However, it remains unclear if CFP1-mediated H3K4 trimethylation is also required for the earliest stages of meiosis in both male and female germ cells. Here, we revealed that Cxxc1 deletion caused a decrease of H3K4me3 levels in spermatocytes after the zygotene stage, impaired double strand breaks (DSBs) repairing, and crossover formation in meiotic prophase. As the results, Cxxc1-deleted spermatocytes failed to complete meiosis and were arrested at the meiosis II. ChIP-seq results revealed that H3K4me3 globally descreased at transcriptional start sites in Cxxc1-null spermatocytes at the leptotene/zygotene and pathytene stages.RNA-seq at different stages revealed an earlier expression of genes within the spermatogenesis pathway in Cxxc1-null spermatocytes. These results indicated that CFP1 is required for H3K4me3 accumulation at the gene promoters of male germ cells and play a key role in regulating programed gene expression that is essential for spermatogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE133636 | GEO | 2020/03/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Integrative Multi-omics Analysis Reveals the Impact of Epigenetic Regulator Cfp1 on male meiosis

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

CFP1 safeguards male meiotic progression by regulating meiotic gene expression

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

RNA-seq analysis of Control and Mps1sKO testis at P10

Project description:Monopolar spindle 1 (Mps1), which plays a critical role in somatic mitosis, has also been revealed to be essential for meiosis I in oocytes. Spermatogenesis is an important process involving successive mitosis and meiosis, but the function of Mps1 in spermatogenesis remains unclear. Here, we generated Mps1 conditional knockout mice and found that Ddx4-cre-driven loss of Mps1 in male mice resulted in depletion of undifferentiated spermatogonial cells and subsequently of differentiated spermatogonia and spermatocytes. In addition, Stra8-cre-driven ablation of Mps1 in male mice led to germ cell loss and fertility reduction. Spermatocytes lacking Mps1 were blocked at the zygotene-to-pachytene transition in prophase of meiosis I, and the expression of many meiotic genes was decreased, while that of apoptotic genes was increased. Moreover, we also detected increased apoptosis in spermatocytes with Mps1 knockout, which may have been the reason why germ cells were lost. Taken together, our findings indicate that Mps1 is required for mitosis of gonocytes and spermatogonia, differentiation of undifferentiated spermatogonia, and progression of meiosis I in spermatocytes.

2021-05-24 | GSE165143 | GEO

DNA/RNA helicase DHX36 is required for late stages of spermatogenesis

Project description:Spermatogenesis is a highly complex developmental process that typically consists of mitosis, meiosis, and spermiogenesis. DNA/RNA helicase DHX36, a unique guanine-quadruplex (G4) resolvase, play crucial roles in a variety of biological processes. We previously showed that DHX36 is highly expressed in male germ cells with the highest level in zygotene spermatocytes. Here, we delete Dhx36 in advanced germ cells with Stra8-GFPCre, and found that a Dhx36 deficiency in the differentiated spermatogonia leads to meiotic defects and abnormal spermiogenesis. These defects in late stages of spermatogenesis arise from dysregulated transcription of G4-harboring genes, which are required for meiosis. Thus, this study reveals that Dhx36 play crucial roles in the late stages of spermatogenesis.

2022-11-24 | GSE218477 | GEO

Screening of genes involved in chromosome segregation in meiosis I

Project description:Prophase I of male meiosis involves dynamic chromosome segregation processes during early spermatogenesis, including synapsis, meiotic recombination, and cohesion. Genetic defects in genes participating in these processes consistently cause reproduction failure in mice. To identify candidate genes responsible for infertility in humans, we performed expression profiling of mouse spermatogenic cells undergoing meiotic prophase I. Cell fractions enriched in spermatogonia, leptotene/zygotene spermatocytes, or pachytene spermatocytes were separately isolated from mouse testes for RNA extraction. To minimize the contamination of other cell types, we fractionated the testicular cells undergoing the first round of spermatogenesis using Percoll gradient procedure. The cell fractions were characterized by morphological analysis by phase contrast microscopy and Nomarski interference microscopy, and then expression of cell lineage- and spermatogenesis stage-specific genes were examined by RT-PCR. The most enriched fractions for spermatogonia (fraction2 from day8), leptotene/zygotene spermatocytes (fraction5 from day12), and pachytene spermatocytes (fraction8 from day15) were subjected to hybridization on Affymetrix microarrays.

2010-03-31 | E-GEOD-19532 | biostudies-arrayexpress

Multiple epigenetic mechanisms and the piRNA pathway enforce LINE1 silencing during adult spermatogenesis

Project description:The Piwi protein Mili and the Piwi-interacting RNA (piRNA) pathway are required to establish L1 DNA methylation during epigenetic reprogramming that accompanies male germ cell development. Although Mili is expressed throughout most of adult spermatogenesis, its function therein remains unknown. We find that Mili displays a hitherto unappreciated dynamic expression profile during spermatogenesis, expressed in the mitotic spermatogonia but absent at the early meiotic stages only to reappear in late zygotene spermatocytes. Here we show using conditional mutagenesis that Mili's endonuclease activity post-transcriptionally cleaves L1 transcripts commencing upon its reappearance in late zygotene spermatocytes even in the presence of normal L1 DNA methylation

2013-07-03 | E-MTAB-1557 | biostudies-arrayexpress

Role of CxxC-finger Protein 1 in the Establishment of Epigenetic Landscapes in Mouse Oocytes

Project description:During oogenesis, oocytes gain competence to accomplish meiotic maturation and prepare for embryonic development following fertilization. Trimethylated histone H3 on lysine-4 (H3K4me3) mediates a wide range of nuclear events during these processes. Oocyte-specific knockout of CxxC-finger protein 1 (CXXC1, also known as CFP1), the chromatin-binding subunit of SETD1 methyltransferase, impairs the H3K4me3 accumulation during murine oogenesis and caused changes in chromatin configurations. This study investigated the changes of genomic H3K4me3 landscapes in oocytes after Cxxc1 knockout, as well as the influences of H3K4me3 changes on other epigenetic marks including DNA methylation, H3K27me3, H2AK119ub1, and H3K36me3. Chromatin immunoprecipitation and sequencing results indicated that H3K4me3 is globally decreased after abolishing Cxxc1, including both the promoter region and the gene body. The results also demonstrate that CXXC1 and another histone H3 methyltransferase MLL2 have nonoverlapping roles in mediating H3K4 trimethylation during oogenesis. In addition, Cxxc1 deletion caused a significant decrease of DNA methylation level in oocytes, and affected H3K27me3 and H2AK119ub1 distributions in the maternal genome, particularly at the regions that have high DNA methylation levels. The changes of epigenetic networks caused by Cxxc1 deletion correlated with transcription changes of the genes in the corresponding genomic regions. Taken together, this study provided mechanistic explanations underlying the phenotypes and molecular defects in Cxxc1 deleted oocytes, and highlighted a role of CXXC1 in orchestrating multiple factors to build up the appropriate epigenetic states of maternal genome during oocyte maturation.

2021-02-04 | GSE159581 | GEO

CXXC1 is not essential for normal DNA double-strand break formation and meiotic recombination in mouse

Project description:In most mammals, including mice and humans, meiotic recombination is determined by the meiosis specific histone methytransferase PRDM9, which binds to specific DNA sequences and trimethylates histone 3 at lysine-4 and lysine-36 at the adjacent nucleosomes. These actions ensure successful DNA double strand break formation and repair that occur on the proteinaceous structure forming the chromosome axis. The process of hotspot association with the axis after their activation by PRDM9 is poorly understood. Previously, we and others have identified CXXC1, an ortholog of S. cerevisiae Spp1 in mammals, as a PRDM9 interactor. In yeast, Spp1 is a histone methyl reader that links H3K4me3 sites with the recombination machinery, promoting DSB formation. Here, we investigated whether CXXC1 has a similar function in mouse meiosis. We created two Cxxc1 conditional knockout mouse to deplete CXXC1 generally in germ cells, and before the onset of meiosis. Surprisingly, male knockout mice were fertile, and the loss of CXXC1 in spermatocytes had no effect on hotspot trimethylation, double-strand break formation or repair. Our results demonstrate that CXXC1 is not an essential link between PRDM9-activated recombination hotspot sites and DSB machinery and that the hotspot recognition pathway in mouse is independent of CXXC1.

2018-08-29 | GSE116336 | GEO

Genome-wide maps of CFP1, RNA Polymerase II and H3K4me3 in mouse brain.

Project description:We report the application of single molecule-based sequencing technology for high-throughput mapping of CFP1, RNA polymerase II and H3K4me3 in mouse brain. By obtaining sequence from chromatin immunoprecipitated DNA, we generated genome-wide binding / chromatin-state maps for mouse brain. We find a good correlation between CFP1 binding and H3K4me3 consistent with it presence in the SetD1 histone methylatransferase complex. Mapped RNA polymerase II colocalised with the majority of CFP1 / H3K4me3 positive CpG islands but not all. This study provides a comprehensive characterisation of the genome wide distribution of a previously uncharacaterised DNA binding factor and suggests a link between DNA base composition and chromatin state. Examination of H3K4me3, RNA PolymeraseII and CFP1 in mouse brain.

2010-04-15 | E-GEOD-18578 | biostudies-arrayexpress

DIS3 is essential for male germ cell meiosis and spermatogenesis in mice

Project description:Male germ cell meiosis is essential for generating haploid spermatozoa in mice. Here, we investigate the essential role of DIS3 in male germ cell meiosis in mice. Conditional inactivation of DIS3 in spermatocytes with Stra8-cre transgenic mice have severely impaired meiotic progression, which results in defective meiosis and spermatogenesis. RNA-seq analysis reveals that Dis3 deficiency causes significant dysregulation of the expression of transcripts in mutant testes. Meiosis-associated genes are significantly decreased in the absence of DIS3. Therefore, we show that DIS3 ribonuclease plays a critical role in germ cell meiosis during spermatogenesis in mice.

2021-07-16 | GSE180197 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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