Molecular mechanism of repression of meiotic recombination around centromeres
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PROVIDER: PRJNA475890 | ENA |
REPOSITORIES: ENA
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Project description:In most eukaryotes, meiotic crossovers are essential for error-free chromosome segregation but are specifically repressed near centromeres to prevent missegregation. Recognized for >85 years, the molecular mechanism of this repression has remained unknown. Meiotic chromosomes contain two distinct cohesin complexes: pericentric complex (for segregation) and chromosomal arm complex (for crossing-over). We show that the pericentric-specific complex also actively represses pericentric meiotic double-strand break (DSB) formation and, consequently, crossovers. The fission yeast pericentric regions contain heterochromatin, removal of which can result in derepression in double-strand break formation and recombination during meiosis. We uncover the mechanism by which fission yeast heterochromatin protein Swi6 (mammalian HP1-homolog) prevents recruitment of activators of meiotic DSB formation such as Rec10. Localizing these missing activators to wild-type pericentromeres bypasses repression and generates abundant crossovers but reduces gamete viability.The molecular mechanism elucidated here likely extends to other species including humans, where pericentric crossovers can result in disorders such as Down syndrome. These mechanistic insights provide new clues to understand the roles played by multiple cohesin complexes, especially in human infertility and birth defects.
2018-06-14 | GSE115726 | GEO
Project description:A chromosome size-dependent bias in meiotic recombination is in place to ensure that homologous chromosome pairing occurs for all chromosomes, including the smallest ones. This bias is clearly detectable during the assembly of the meiotic protein axis, the structure that compacts meiotic chromosomes and promotes recombination.To investigate the origin of the size bias, we mapped genome-wide occupancy of the meiotic axis protein Red1 in yeast strains containing chromosome fusions and synthetic chromosomes. Meiosis studies of the fusion and synthetic chromosomes further revealed that core centromeres influence the deposition of the axial element protein Red1 over distances >100kb, while pericentromeric regions co-evolved to reduce Red1 binding near centromeres and spread out Red1 along the chromosomes.
2021-05-21 | GSE114731 | GEO
Project description:Meiotic homologous recombination is a critical DNA-templated event for sexually-reproducing organisms. It is initiated by a programmed formation of DNA double strand breaks (DSBs), mainly formed at recombination hotspots, and is, like all other DNA-related processes, under great influence of chromatin structure. For example, local chromatin around hotspots directly impacts DSB formation. In addition, DSB is proposed to occur in a higher-order chromatin architecture termed “axis-loop”, in which many loops protrude from proteinaceous axis. Despite many recent insightful studies, still much remains unknown about how meiotic DSBs are generated in chromatin structure. Here, we show that the highly conserved histone H2A variant H2A.Z promotes meiotic DSB formation in fission yeast. Subsequent investigation revealed that H2A.Z is neither enriched around hotspots nor axis sites, and that transcript levels of DSB-promoting factors were maintained in the absence of H2A.Z. Instead, we found that H2A.Z facilitates chromatin binding of various proteins required for DSB formation. Strikingly, artificial tethering of one of such proteins, Rec10, to chromatin partially restored DSB reduction in H2A.Z-lacking cells. Based on these, we conclude that fission yeast H2A.Z promotes initiation of meiotic recombination partly through delivering DSB-related proteins onto chromatin.
2017-10-24 | GSE81776 | GEO
Project description:Meiotic homologous recombination is a critical DNA-templated event for sexually-reproducing organisms. It is initiated by a programmed formation of DNA double strand breaks (DSBs), mainly formed at recombination hotspots, and is, like all other DNA-related processes, under great influence of chromatin structure. For example, local chromatin around hotspots directly impacts DSB formation. In addition, DSB is proposed to occur in a higher-order chromatin architecture termed “axis-loop”, in which many loops protrude from proteinaceous axis. Despite many recent insightful studies, still much remains unknown about how meiotic DSBs are generated in chromatin structure. Here, we show that the highly conserved histone H2A variant H2A.Z promotes meiotic DSB formation in fission yeast. Subsequent investigation revealed that H2A.Z is neither enriched around hotspots nor axis sites, and that transcript levels of DSB-promoting factors were maintained in the absence of H2A.Z. Instead, we found that H2A.Z facilitates chromatin binding of various proteins required for DSB formation. Strikingly, artificial tethering of one of such proteins, Rec10, to chromatin partially restored DSB reduction in H2A.Z-lacking cells. Based on these, we conclude that fission yeast H2A.Z promotes initiation of meiotic recombination partly through delivering DSB-related proteins onto chromatin.
2017-10-24 | GSE81775 | GEO
Project description:Meiotic chromosome architecture called M-bM-^@M-^\axis-loop structuresM-bM-^@M-^] and histone modifications have been demonstrated to regulate the Spo11-dependent formation of DNA double-strand breaks (DSBs) that trigger meiotic recombination. Using genome-wide chromatin immunoprecipitation (ChIP) analyses followed by deep sequencing, we compared the genome-wide distribution of the axis protein Rec8 (the kleisin subunit of meiotic cohesin) with that of oligomeric DNA covalently bound to Spo11, indicative of DSB sites. The frequency of DSB sites is overall constant between Rec8 binding sites. However, DSB cold spots are observed in regions spanning M-BM-10.8 kb around Rec8 binding sites. The axis-associated cold spots are not due to exclusion of Spo11 localization from the axis, since ChIP experiments revealed that substantial Spo11 persists at Rec8 binding sites during DSB formation. Spo11 fused with Gal4 DNA binding domain (Gal4BD-Spo11) tethered in close proximity (M-bM-^IM-$0.8 kb) to Rec8 binding sites hardly forms meiotic DSBs, in contrast with other regions. In addition, H3K4 tri-methylation (H3K4me3) remarkably decreases at Rec8 binding sites. These results suggest that reduced histone H3K4me3 in combination with inactivation of Spo11 activity on the axis discourages DSB hot spot formation. ChIP-chip analysis of Rec8 on fission yeast meiotic chromosomes
2014-03-31 | E-GEOD-52858 | biostudies-arrayexpress
Project description:Meiotic chromosome architecture called M-bM-^@M-^\axis-loop structuresM-bM-^@M-^] and histone modifications have been demonstrated to regulate the Spo11-dependent formation of DNA double-strand breaks (DSBs) that trigger meiotic recombination. Using genome-wide chromatin immunoprecipitation (ChIP) analyses followed by deep sequencing, we compared the genome-wide distribution of the axis protein Rec8 (the kleisin subunit of meiotic cohesin) with that of oligomeric DNA covalently bound to Spo11, indicative of DSB sites. The frequency of DSB sites is overall constant between Rec8 binding sites. However, DSB cold spots are observed in regions spanning M-BM-10.8 kb around Rec8 binding sites. The axis-associated cold spots are not due to exclusion of Spo11 localization from the axis, since ChIP experiments revealed that substantial Spo11 persists at Rec8 binding sites during DSB formation. Spo11 fused with Gal4 DNA binding domain (Gal4BD-Spo11) tethered in close proximity (M-bM-^IM-$0.8 kb) to Rec8 binding sites hardly forms meiotic DSBs, in contrast with other regions. In addition, H3K4 tri-methylation (H3K4me3) remarkably decreases at Rec8 binding sites. These results suggest that reduced histone H3K4me3 in combination with inactivation of Spo11 activity on the axis discourages DSB hot spot formation. ChIP-seq analyses of Rec8, Spo11, and Gal4BD-Spo11 on budding yeast meiotic chromosomes M-bM-^@M-" Distribution of Rec8 in wt and Gal4BD-Spo11-expressing cells at 4h after meiotic induction M-bM-^@M-" Distribution of Spo11 at 3h, 4h, and 5h after meiotic induction M-bM-^@M-" Distribution of Gal4BD-Spo11 at 0h after meiotic induction
2014-03-31 | E-GEOD-52862 | biostudies-arrayexpress
Project description:Temperature is key for biological activities, but its role in meiotic recombination processes is less known. Here, we uncovered the patterns of meiotic recombination by monitoring the double strands DNA breaks in diploid strain ZK5 cells cultured at 14ºC, 30ºC, and 37ºC.
2017-07-04 | GSE100741 | GEO
Project description:Temperature is key for biological activities, but its role in meiotic recombination processes is less known. Here, we uncovered the patterns of meiotic recombination by monitoring the genotypes of diploid strain JSC22-1-derived spores formed at 14ºC, 30ºC, and 37ºC. These spores were analyzed by whole genome SNP microarray that can examine about 13,000 SNPs distinguishing W303-1A and YJM789 sequences throughout the genome.
2017-06-06 | GSE97667 | GEO
Project description:Meiotic recombination differs between males and females, however, when and how these differences are established is unknown. We identify extensive sex differences at recombination initiation by mapping hotspots of meiotic DNA double strand breaks in male and female mice. Contrary to past findings in humans, few hotspots are used uniquely in either sex. Instead, grossly different recombination landscapes result from up to 15-fold differences in hotspot use between males and females. Indeed, most recombination occurs at sex-biased hotspots. Sex biased hotspots appear to be partly determined by chromosome structure, and DNA methylation, absent in females at the onset of meiosis, plays a substantial role. Sex differences are also evident later in meiosis as the repair frequency of distal meiotic breaks as crossovers diverges in males and females. Suppression of distal crossovers may help to minimize age-related aneuploidy that arises due to cohesion loss during dictyate arrest in females.
2018-09-20 | GSE99921 | GEO
Project description:Several protein ensembles facilitate meiotic crossover recombination and the associated process of synaptonemal complex (SC) assembly during meiosis. We have employed proximity labeling as a phenotyping tool to investigate functional requirements for spatial relationships between meiotic recombination and SC proteins in S. cerevisiae, and to gain deeper insight into the molecular deficits of crossover-deficient meiotic mutants. We find that recombination initiation and synaptonemal complex structures are dispensable for proximity labeling of the Zip3 E3 ligase by components of the ZZS ensemble (Zip2, Zip4 and Spo16) but enzymes associated with early steps in recombination are required for Zip3 proximity labeling by MutSg, consistent with the possibility that MutSg joins Zip3 only after a specific recombination intermediate has been generated. Proximity labeling furthermore suggests that a key defect of crossover-defective, SC-proficient zip1 separation-of-function mutants is a failure to assemble an early recombination ensemble where MutSg can properly engage Zip3. We also find that the SC structural protein Ecm11 is proximity labeled by ZZS proteins in a Zip4-dependent and Zip1-independent manner, but by Zip3 and Msh4 at least in part via a distinct pathway that relies on Zip1. Finally, streptavidin pulldown followed by mass spectrometry on eleven proximity labeling strains uncovered shared proximity targets of SC and crossover-associated proteins, some of which have not yet been implicated in meiotic recombination or SC formation highlighting the potential of proximity labeling as a discovery tool.
2024-10-02 | PXD053621 | Pride