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Physical basis for long-distance communication along meiotic chromosomes (ChIP-chip))

ABSTRACT: Viable gamete formation requires segregation of homologous chromosomes connected, in most species, by crossovers. DNA double-strand break (DSB) formation and the resulting crossovers are regulated at multiple levels to prevent overabundance along chromosomes. Meiotic cells coordinate these events between distant sites, but the physical basis of long-distance chromosomal communication has been unknown. We show that DSB hotspots up to ~200 kb (~35 cM) apart form clusters via hotspot-binding proteins Rec25 and Rec27 in fission yeast. Clustering coincides with hotspot competition and interference over similar distances. Without Tel1 (ATM tumor-suppressor homolog), DSB and crossover interference become negative, reflecting coordinated action along a chromosome. These results indicate that DSB hotspots within a limited chromosomal region and bound by their protein determinants form a clustered structure that, via Tel1, allows only one DSB per region. Such a “roulette” process among clusters explains the observed pattern of crossover interference in fission yeast. Key structural and regulatory components of clusters are phylogenetically conserved, suggesting conservation of this vital regulation. Based on these observations, we discuss variations on a model in which clustering and competition between DSB sites leads to DSB interference and in turn produces crossover interference.

ORGANISM(S): Schizosaccharomyces pombe

PROVIDER: GSE119920 | GEO | 2018/09/17

REPOSITORIES: GEO

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Physical basis for long-distance communication along meiotic chromosomes (ChIP-seq)

Project description:Viable gamete formation requires segregation of homologous chromosomes connected, in most species, by crossovers. DNA double-strand break (DSB) formation and the resulting crossovers are regulated at multiple levels to prevent overabundance along chromosomes. Meiotic cells coordinate these events between distant sites, but the physical basis of long-distance chromosomal communication has been unknown. We show that DSB hotspots up to ~200 kb (~35 cM) apart form clusters via hotspot-binding proteins Rec25 and Rec27 in fission yeast. Clustering coincides with hotspot competition and interference over similar distances. Without Tel1 (ATM tumor-suppressor homolog), DSB and crossover interference become negative, reflecting coordinated action along a chromosome. These results indicate that DSB hotspots within a limited chromosomal region and bound by their protein determinants form a clustered structure that, via Tel1, allows only one DSB per region. Such a “roulette” process among clusters explains the observed pattern of crossover interference in fission yeast. Key structural and regulatory components of clusters are phylogenetically conserved, suggesting conservation of this vital regulation. Based on these observations, we discuss variations on a model in which clustering and competition between DSB sites leads to DSB interference and in turn produces crossover interference.

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Numerical and Spatial Patterning of Yeast Meiotic DNA Breaks by Tel1

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2016-07-22 | E-GEOD-84696 | biostudies-arrayexpress

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2016-07-22 | GSE84696 | GEO

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The conserved SUMO ligase Zip3 protein associates differentially with meiotic double-strand break sites and reveals regional variations in the outcome of meiotic recombination

Project description:In meiosis, an excess number of DNA double-strand breaks (DSBs), the initiating DNA lesion, is formed compared to the number of crossovers, one of their repair products that creates the physical links between homologs and allows their correct segregation. It is not known if all DSB hotspots are also crossover hotspots, or if the ratio between DSB and crossovers varies with the chromosomal location. Here, to systematically investigate variation in the DSB/crossover ratio, we have established the genome-wide map of the Zip3 protein binding sites in budding yeast meiosis. We show that Zip3 associates with DSB sites when these are engaged into repair by crossing over, and that Zip3 binding frequency at DSB reflects its tendency to be repaired as a crossover. We further show that the relative amount of Zip3 per DSB varies with the chromosomal location and identify chromosomal features associated with high or low Zip3 per DSB ratio. Among these is the negative regulation by proximity to a centromere and positive by the proximity to axis-associated sequences. This work opens interesting perspectives to understand the role of these extra DSB that are not frequently used for crossover and our findings may extend to mammals that have a large excess of DSB compared to crossovers.

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The conserved SUMO ligase Zip3 protein associates differentially with meiotic double-strand break sites and reveals regional variations in the outcome of meiotic recombination

2013-12-18 | E-GEOD-40563 | biostudies-arrayexpress

Histone H3 lysine9 acetylation, rather than lysine4 trimethylation, marks meiotic recombination hotspots and promotes recombination initiation in fission yeast

2013-03-07 | GSE31648 | GEO

Meiotic prophase length modulates Tel1-dependent DNA double-strand break interference

Project description:During meiosis, genetic recombination is initiated by the formation of many DNA double-strand breaks (DSBs) catalysed by the evolutionarily conserved topoisomerase-like enzyme, Spo11, in preferred genomic sites known as hotspots. DSB formation activates the Tel1/ATM DNA damage responsive (DDR) kinase, locally inhibiting Spo11 activity in adjacent hotspots via a process known as DSB interference. Intriguingly, in S. cerevisiae, over short genomic distances (<15 kb), Spo11 activity displays characteristics of concerted activity or clustering, wherein the frequency of DSB formation in adjacent hotspots is greater than expected by chance. We have proposed that clustering is caused by a limited number of sub-chromosomal domains becoming primed for DSB formation. Here, we provide evidence that DSB clustering is abolished when meiotic prophase timing is extended via deletion of the NDT80 transcription factor. We propose that extension of meiotic prophase enables most cells, and therefore most chromosomal domains within them, to reach an equilibrium state of similar Spo11-DSB potential, reducing the impact that priming has on estimates of coincident DSB formation. Consistent with this view, when Tel1 is absent but Ndt80 is present and thus cells are able to rapidly exit meiotic prophase, genome-wide maps of Spo11-DSB formation are skewed towards pericentromeric regions and regions that load pro-DSB factors early—revealing regions of preferential priming—but this effect is abolished when NDT80 is deleted. Our work highlights how the stochastic nature of Spo11-DSB formation in individual cells within the limited temporal window of meiotic prophase can cause localised DSB clustering—a phenomenon that is exacerbated in tel1∆ cells due to the dual roles that Tel1 has in DSB interference and meiotic prophase checkpoint control.

2023-10-18 | GSE245327 | GEO

Histone H3 lysine9 acetylation, rather than lysine4 trimethylation, marks meiotic recombination hotspots and promotes recombination initiation in fission yeast

Project description:Histone modifications are associated with meiotic recombination hotspots, discrete sites with augmented recombination frequency. For example, trimethylation of histone H3 lysine4 (H3K4me3) marks most hotspots in budding yeast and mouse. Modified histones are known to regulate meiotic recombination partly by promoting DNA double strand break (DSB) formation, but the role and precise landscape of histone modifications at hotspots remain unclear. Here, we studied hotspot-associated modifications in fission yeast and found general features: acetylation of H3 lysine9 (H3K9ac) is strikingly elevated, and H3K4me3 is not significantly enriched. Remarkably, elimination of H3K9ac reduced binding of the DSB-inducing enzyme Rec12 and DSB at hotspots. We also found that the H3K4 metyltransferase Set1 promotes DSB formation at some loci, but it restricts Rec12 binding to hotspots. These results suggest that H3K9ac rather than H3K4me3 is a hotspot-associated mark involved in meiotic DSB formation in fission yeast. S.pombe cells in a pat1-114 background were induced to enter meiosis by the haploid meiosis system, and harvested one hour after the induction. ChIP were performed using anti-H3Cter, H3K9ac, -H3K14ac and -H3K4me3 antibodies. pat1-114 rad50S rec12+-FLAG cells in a wild type, H3K9A or set1+ deletion background were induced to enter meiosis by the haploid meiosis system, and harvested five hours after the induction. ChIP were performed using anti-FLAG antibodies.

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