Meiotic crossover analysis from F1 mouse sperm
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PROVIDER: PRJEB85615 | ENA |
REPOSITORIES: ENA
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Project description:Meiotic crossover formation requires the stabilization of early recombination intermediates by a set of proteins and occurs within the environment of the chromosome axis, a structure important for the regulation of meiotic recombination events. The molecular mechanisms underlying and connecting crossover recombination and axis localization are elusive. Here, we identified the ZZS (Zip2–Zip4–Spo16) complex, required for crossover formation, which carries two distinct activities: one provided by Zip4, which acts as hub through physical interactions with components of the chromosome axis and the crossover machinery, and the other carried by Zip2 and Spo16, which preferentially bind branched DNA molecules in vitro. We found that Zip2 and Spo16 share structural similarities to the structure-specific XPF–ERCC1 nuclease, although it lacks endonuclease activity. The XPF domain of Zip2 is required for crossover formation, suggesting that, together with Spo16, it has a noncatalytic DNA recognition function. Our results suggest that the ZZS complex shepherds recombination intermediates toward crossovers as a dynamic structural module that connects recombination events to the chromosome axis. The identification of the ZZS complex improves our understanding of the various activities required for crossover implementation and is likely applicable to other organisms, including mammals.
2018-02-14 | GSE103877 | GEO
Project description:Programmed DNA double-strand breaks (DSBs) initiate meiotic recombination and their subsequent repair culminates in crossover (CO) formation. COs result from the asymmetric cleavage of double-Holliday junction (dHJ) intermediates, that requires the MutLγ endonuclease and a non-catalytic function of Exo1, an activity essential for fertility but at risk of generating unwanted chromosome rearrangements. Here we show how crossover formation by MutLγ is activated at the right time and at the right place. MutLγ forms a constitutive complex with Exo1, and in meiotic cells transiently contacts the upstream MutSγ (Msh4-Msh5) heterodimer. MutLγ associates with DSB hotspots only once recombination intermediates have been stabilized and engaged in the crossover repair pathway. MutLγ-Exo1 is recruited to DSB hotspots independently of the polo-like Cdc5 kinase, but to activate dHJ resolution, Cdc5 is recruited to the recombination intermediates and interacts individually with both MutLγ and Exo1, suggesting their direct modification. in vivo, MutLγ occupancy is restrained on recombination intermediates, and MutLγ associates with the vast majority of DSB hotspots, but at a lower frequency in centromeres, consistent with a strategy to reduce at-risk crossover events in these regions, and in late replicating regions. Our data highlight the tight temporal and spatial control of the activity of this constitutive, potentially harmful, nuclease.
2020-01-15 | GSE133108 | GEO
Project description:Programmed DNA double-strand breaks (DSBs) initiate meiotic recombination and their subsequent repair culminates in crossover (CO) formation. COs result from the asymmetric cleavage of double-Holliday junction (dHJ) intermediates, that requires the MutLγ complex together with a non-catalytic function of Exo1, an activity essential for fertility but at risk of generating unwanted chromosome rearrangements. Here we show how crossover formation by MutLγ is activated at the right time and at the right place. MutLγ forms a constitutive complex with Exo1, and in meiotic cells transiently contacts the upstream MutSγ (Msh4-Msh5) heterodimer. MutLγ associates with DSB hotspots at a late step in the recombinational repair, once recombination intermediates have been stabilized and engaged in the crossover repair pathway. MutLγ-Exo1 is recruited to DSB hotspots independently of the polo-like Cdc5 kinase, but to activate dHJ resolution, Cdc5 is recruited to the recombination intermediates and interacts individually with both MutLγ and Exo1, suggesting their direct modification. in vivo, MutLγ occupancy is restrained on recombination intermediates, and genome-wide, MutLγ associates with the vast majority of DSB hotspots, but at a lower frequency in centromeres, consistent with a strategy to reduce at-risk crossover events in these regions, and in late replicating regions. Our data highlight the highly temporally and spatially control of the activity of this constitutive, potentially harmful, nuclease
2019-12-01 | GSE132850 | GEO
Project description:Meiotic crossover landscape within RAC1 disease resistance gene
| PRJEB24064 | ENA
Project description:Meiotic recombination is initiated by programmed DNA double-strand breaks (DSBs) and proceeds via binding of RPA, RAD51 and DMC1 to single-stranded DNA (ssDNA) substrates created after the formation of DSBs. Here, we report high-resolution in vivo maps of RPA and RAD51 binding in meiosis, mapping their binding locations and lifespans in a B6 and a genetically modified B6xCAST F1 mouse. We ascribe signals separately to the individual homologous chromosomes in the hybrid mouse, thereby separating the signal of binding to the chromosome where DSBs occurred and the chromosome that was used as template for repair. Together with super-resolution microscopy and DMC1 binding maps, we show that DMC1 and RAD51 have distinct spatial localization on ssDNA: whereas DMC1 binds near the break-site, RAD51 binds away from it. We characterize the D-loop, a critical intermediate bound by RPA, in vivo. These data show that DMC1, not RAD51, performs strand exchange in mammalian meiosis. We find that the localisation of D-loop intermediates is similar in crossover and non-crossover pathways, with a longer lifespan for crossover-destined intermediates. These findings answer long-standing questions about the molecular intermediates of recombination.
2020-06-30 | GSE143582 | GEO
Project description:Pregnant C3H mice were given tap water (control group) and tap water containing 85 ppm sodium arsenite from gestational day 8 to 18 (arsenic group), respectively. The DNA methylomes of sperm of F1 mice were investigated by RRBS method. The results showed that gestational arsenic exposure increased hypomethylated cytosines in the F1 sperm genome. The present study has indicated environmental impacts on sperm DNA methylome establishment.
2020-12-08 | GSE150500 | GEO
Project description:To study recombination at the fine-scale, we used high-throughput sequencing of 300 to 1,000 crossovers within the RAC1 R gene hotspot. This revealed focused intragenic crossovers, overlapping exons encoding the TIR, NBS and LRR domains. To examine the role of recombination pathways, we repeated this experiment in recq4a recq4b, fancm and recq4a recq4b fancm mutants. Finally, in order to investigate how varying patterns of interhomolog divergence influence local patterns of crossover frequency, we repeated RAC1 pollen typing sequencing in different F1 hybrids.
2018-07-01 | E-MTAB-6333 | biostudies-arrayexpress
Project description:Using microarrays to genotype the parental origin of progeny resulting from a cross between S96 and YJM789 yeast strains, we mapped the distribution of crossovers that occurred during meiosis. Knowledge of the crossover distribution allowed us to assess changes in crossover control in wild type and mutant strains. The S96 strain is a S288 derivative and thus its DNA sequence has high homology to the oligo sequences used to create the S98 Affymetrix Gene chip. The YJM789 strain is ~ 0.6% divergent from S288. Keywords: wild type and mutant analysis
2008-09-16 | GSE12170 | GEO
Project description:We report 2,649 crossover breakpoints identified by single-cell DNA sequencing of 217 sperm in a B6xCAST F1 mouse, which is heterozygous at Prdm9, with one wild-type CAST allele and one allele found in human populations (bred from a genetically engineered mother, Davies et al Nature 2012). Separately, we have reported testis DMC1 enrichment in the same mouse (GSE124991). We also infer H3K4me3 intensities at DMC1 hotspots, based on the raw H3K4me3 ChIP-seq data published under GSE119727 (Li et al). We identify several factors, including PRDM9 binding on the repair-template homologue, telomere proximity and local GC-content, that affect the probability that a DSB is repaired as a crossover. We further show that these factors also influence the time it takes for the site of a DSB to find and engage its homologue, with rapidly-engaging sites being more likely to be repaired as crossovers.
2019-03-18 | GSE125326 | GEO
Project description:Birth cohort studies and experimental investigations in animals link gestational diabetes mellitus (GDM) with impaired cognitive performance in the first filial generation (F1). We found that intrauterine hyperglycemia exposure resulted in behavior abnormality and cognitional functional disorder of both F1- and F2-GDM male mice. Methylome of sperm of F1 adult male mice from control pregnant mice (F1-C) and GDM pregnant mice (F1-GDM) revealed differentially methylated genes enriched in neurodevelopmental process.
2021-08-25 | GSE142502 | GEO