Histone methyltransferase PRDM9 is not essential for meiosis in male mice
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ABSTRACT:
PROVIDER: PRJNA432219 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6653240_1.fastq.gz | Fastqsanger.gz | |||
| SRR6653240_2.fastq.gz | Fastqsanger.gz | |||
| SRR6653242_1.fastq.gz | Fastqsanger.gz | |||
| SRR6653242_2.fastq.gz | Fastqsanger.gz | |||
| SRR6653243_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:A hallmark of meiosis is the rearrangement of parental alleles to assure genetic diversity in gametes. These chromosome rearrangements are mediated by the repair of programmed DNA double-strand-breaks (DSBs) as genetic crossovers between parental homologs. In mice, humans, and many other mammals, meiotic DSB occur primarily at hotspots, determined by sequence-specific binding of the PRDM9 protein. Without PRDM9, meiotic DSBs occur near gene promoters and other functional sites. Studies in a limited number of mouse strains showed that functional PRDM9 is required to complete meiosis, but despite its apparent importance, Prdm9 has been repeatedly lost across many animal lineages. Both the reason for mouse sterility in the absence of PRDM9 and the mechanism by which Prdm9 can be lost remain unclear. Here, we explore if mice can tolerate the loss of Prdm9. By generating Prdm9 functional knockouts in an array of genetic backgrounds, we observe a wide range of fertility phenotypes and ultimately demonstrate that PRDM9 is not required for completion of meiosis. Although DSBs still form at a common subset of functional sites in all mice lacking PRDM9, meiotic outcomes differ substantially. We speculate that DSBs at functional sites are difficult to repair as a crossover and that by increasing the efficiency of crossover formation at these sites, genetic modifiers of recombination rates can allow for meiotic progression. This model implies that species with a sufficiently high recombination rate may lose Prdm9 yet remain fertile.
2019-06-07 | GSE109874 | GEO
Project description:The programmed formation of hundreds DNA double strand breaks (DSBs) is essential for proper meiosis and fertility. In mice and humans, the location of these breaks is determined by the meiosis-specific protein PRDM9, through the DNA binding specificity of its zinc finger domain. PRDM9 also has methyltransferase activity. Here, we show that this activity is required for H3K4me3 and H3K36me3 deposition and for DSB formation at PRDM9 binding sites. By analyzing mice that express two PRDM9 variants with distinct DNA binding specificities, we reveal severalthe basic principles of PRDM9-dependent DSB site determination, in which an excess of sites are designated through PRDM9 binding and subsequent histone methylation, from which a subset are selected for DSB formation.
2018-02-09 | GSE108953 | GEO
Project description:Homologous recombination is required for proper segregation of homologous chromosomes during meiosis. It predominantly occurs at recombination hotspots that are defined by the DNA binding specificity of the PRDM9 protein. PRDM9 contains three domains which are typically different families of proteins involved in regulation of transcription in other proteins, yet, the role of PRDM9 in gene expression control has not been evaluated. Here we analyze the germline transcriptome of the Prdm9-/- male mice in comparison to Prdm9+/+ males and find no apparent differences in the mRNA and miRNA profiles. We further explore the role of PRDM9 in meiosis by analyzing the activity of PRDM9 lacking effect of the KRAB, SSXRD and post-SET zinc finger domains deletion mutants in a cell expression system and the KRAB domain deletion in mice. We found that although the post-SET zinc finger and the KRAB domains are not essential for the methyltransferase activity of PRDM9 in a cell culture expression systemin vitro, mice lacking the KRAB domain mutant mice domain show only residual PRDM9 methyltransferase activity and undergo meiotic arrest. In aggregate, our data indicate that these domains that are classically involved in gene regulation do not serve that role in PRDM9, but instead are involved in PRDM9 function has likely diverged from the typical function of a transcription factor and adapted the new role in setting the proper chromatin environment for initiation and completion of homologous recombination.
2018-04-27 | GSE104850 | GEO
Project description:PRDM9 methyltransferase is essential for meiotic DSB formation
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Project description:Protein Arginine Methyltransferase 1 is Essential for the Meiosis of Male Germ Cells
| PRJNA736299 | ENA
Project description:A hallmark of meiosis is the rearrangement of parental alleles to ensure genetic diversity in the gametes. These chromosome rearrangements are mediated by the repair of programmed DNA double-strand breaks (DSBs) as genetic crossovers between parental homologs. In mice, humans, and many other mammals, meiotic DSBs occur primarily at hotspots, determined by sequence-specific binding of the PRDM9 protein. Without PRDM9, meiotic DSBs occur near gene promoters and other functional sites. Studies in a limited number of mouse strains showed that functional PRDM9 is required to complete meiosis, but despite its apparent importance, Prdm9 has been repeatedly lost across many animal lineages. Both the reason for mouse sterility in the absence of PRDM9 and the mechanism by which Prdm9 can be lost remain unclear. Here, we explore whether mice can tolerate the loss of Prdm9 By generating Prdm9 functional knockouts in an array of genetic backgrounds, we observe a wide range of fertility phenotypes and ultimately demonstrate that PRDM9 is not required for completion of male meiosis. Although DSBs still form at a common subset of functional sites in all mice lacking PRDM9, meiotic outcomes differ substantially. We speculate that DSBs at functional sites are difficult to repair as a crossover and that by increasing the efficiency of crossover formation at these sites, genetic modifiers of recombination rates can allow for meiotic progression. This model implies that species with a sufficiently high recombination rate may lose Prdm9 yet remain fertile.
| S-EPMC6633264 | biostudies-literature
Project description:Meiotic recombination starts with the formation of DNA double-strand breaks (DSBs) at specific genomic locations that correspond to PRDM9-binding sites. The molecular steps occurring from PRDM9 binding to DSB formation are unknown. Using proteomic approaches to find PRDM9 partners, we identified HELLS, a member of the SNF2-like family of chromatin remodelers. Upon functional analyses during mouse male meiosis, we demonstrated that HELLS is required for PRDM9 binding and DSB activity at PRDM9 sites. However, HELLS is not required for DSB activity at PRDM9-independent sites. HELLS is also essential for 5-hydroxymethylcytosine (5hmC) enrichment at PRDM9 sites. Analyses of 5hmC in mice deficient for SPO11, which catalyzes DSB formation, and in PRDM9 methyltransferase deficient mice reveal that 5hmC is triggered at DSB-prone sites upon PRDM9 binding and histone modification, but independent of DSB activity. These findings highlight the complex regulation of the chromatin and epigenetic environments at PRDM9-specified hotspots.
2020-11-19 | GSE145768 | GEO
Project description:PRDM9 specifies the sites of meiotic DNA double strand break that initiate meiotic recombination in mice and humans. PRDM9 is known to bind to specific DNA sequences with its DNA binding domain, to induce H3K4me3 and H3K36me3 to adjacent nucleosomes through its methyltransferase activity, and to recruit or activate the meiotic DSB machinery. To understand how PRDM9 executes these various steps, we set up to identify its partners. This was performed by a proteomic approach where protein extracts from mouse testis were immunoprecipitated with anti-PRDM9 antibody for mass spectrometry analysis.
2020-12-03 | PXD017337 | Pride
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
Project description:Interrogating the functions of PRDM9 domains in meiosis
| PRJNA413989 | ENA