Genomic and chromatin features shaping meiotic double-strand break formation and repair in mice

Yamada, Shintaro; Kim, Seo Young; Tischfield, Sam E.; Jasin, Maria; Lange, Julian; Keeney, Scott

doi:10.1080/15384101.2017.1361065

Cited by 57 publications

(57 citation statements)

References 109 publications

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“…However, Kac and Kcro positively correlate with 20 one another while exhibiting opposite directions in the linear model, and could be counteracting each other in the model without being truly associated with crossover hotness. A few other well established marks such as H3K4me3, H3K27ac and H3K36me3 (37,38) are not statistically significant in our model. It is possible that their effects have been represented by Spo11 break sites and are thus not significant given that Spo11 is already in the model.…”

Section: Discussioncontrasting

confidence: 64%

High-throughput mapping of meiotic crossover and chromosome mis-segregation events in interspecific hybrid mice

Yin

Jiang²,

Berletch

et al. 2018

Preprint

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We developed "sci-LIANTI", a high-throughput, high-coverage single-cell DNA sequencing method that combines single-cell combinatorial indexing ("sci") and linear amplification via transposon insertion ("LIANTI"). To characterize rare chromosome missegregation events in male meiosis and their relationship to the landscape of meiotic crossovers, we applied sci-LIANTI to profile the genomes of 6,928 sperm and sperm precursors from 20 infertile, interspecific F1 male mice. From 1,663 haploid and 292 diploid cells, we mapped 24,672 crossover events and identified genomic and epigenomic contexts that influence crossover hotness. Surprisingly, we observed frequent mitotic chromosome segregation during meiosis. Moreover, segregation during meiosis in individual cells was highly biased towards either mitotic or meiotic events. We anticipate that sci-LIANTI can be applied to fully 25 characterize various recombination landscapes, as well as to other fields requiring highthroughput, high-coverage single-cell genome sequencing.One Sentence Summary: Single-cell genome sequencing maps crossover and non-meiotic chromosome segregation during spermatogenesis in interspecific hybrid mice. 30

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Section: Discussioncontrasting

confidence: 64%

High-throughput mapping of meiotic crossover and chromosome mis-segregation events in interspecific hybrid mice

Yin

Jiang²,

Berletch

et al. 2018

Preprint

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“…How recombination machinery accesses a chromatinized donor is not well understood (Neale and Keeney 2006;Kobayashi et al 2016). Average profiles around hotspots of H3K4me3 and H3K36me3 chromatin immunoprecipitation (ChIP) sequencing data show peaks of methylated nucleosome coverage flanking PRDM9 binding sites and the main cluster of DSB positions (Figure 4A) (Baker et al 2014;Lange et al 2016;Powers et al 2016;Yamada et al 2017). An implication is that the strand exchange machinery frequently invades segments of the homologous donor DNA that contain these methylated nucleosomes (if PRDM9 acted on the donor as well as the broken chromosome) plus additional flanking nucleosomes further away (Figure 4B).…”

Section: Prdm9-dependent Modulation Of Local Chromatin Accessibilitymentioning

confidence: 99%

Molecular structures and mechanisms of DNA break processing in mouse meiosis

Yamada

Hinch

Kamido

et al. 2019

Preprint

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Exonucleolytic resection, critical to repair double-strand breaks (DSBs) by recombination, is not well understood, particularly in mammalian meiosis. Here, we define structures of resected DSBs in mouse spermatocytes genome-wide at nucleotide resolution. Resection tracts averaged 1100 nucleotides, but with substantial fine-scale heterogeneity at individual hotspots. Surprisingly, EXO1 is not the major 5′→3′ exonuclease, but the DSB-responsive kinase ATM proved a key regulator of both initiation and extension of resection. In wild type, apparent intermolecular recombination intermediates clustered near to but offset from DSB positions, consistent with joint molecules with incompletely invaded 3′ ends. Finally, we provide evidence for PRDM9-dependent chromatin remodeling leading to increased accessibility at recombination sites. Our findings give insight into the mechanisms of DSB processing and repair in meiotic chromatin.

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“…This results in new combinations of alleles in the next generation that can generate novel phenotypic variation, which is the raw material for both natural and artificial selection [1][2][3] . In most organisms, the locations of COs along chromosomes do not form a random distribution [4][5][6][7][8][9][10][11] . Thus, the local CO rate governs the types of allelic combinations that can arise through sexual reproduction.…”

Section: Introductionmentioning

confidence: 99%

Linked-read sequencing of gametes allows efficient genome-wide analysis of meiotic recombination

Sun

Rowan

Flood

et al. 2018

Preprint

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Meiotic crossovers (COs) ensure proper chromosome segregation and redistribute the genetic variation that is transmitted to the next generation. Existing methods for CO identification are challenged by large populations and the demand for genome-wide and fine-scale resolution. Taking advantage of linked-read sequencing, we developed a highly efficient method for genome-wide identification of COs at kilobase resolution in pooled recombinants. We first tested this method using a pool of Arabidopsis F 2 recombinants, and obtained results that recapitulated those identified from the same plants using individual whole-genome sequencing. By applying this method to a pool of pollen DNA from a single F 1 plant, we established a highly accurate CO landscape without generating or sequencing a single recombinant plant. The simplicity of this approach now enables the simultaneous generation and analysis of multiple CO landscapes and thereby allows for efficient comparison of genotypic and environmental effects on recombination, accelerating the pace at which the mechanisms for the regulation of recombination can be elucidated. CO detection using linked-read sequencing RESULTS CO breakpoint detection from bulk recombinantsTo establish a set of COs for verifying our method, we first performed whole-genome sequencing of 50 individual F 2 plants derived from a cross of two of the best-studied inbred lab strains of Arabidopsis, Col-0 and Ler and used the haplotype reconstruction software TIGER 33 to determine a benchmark set of 400 COs across all 50 genomes (Fig. 1 ; Materials and Methods;Supplementary Tables 1 and 2).We then bulked the identical 50 F 2 plants by pooling individual leaves of comparable size and extracting high molecular weight (HMW) DNA 37 (Fig. 1). After size selection and quality control ( Supplementary Fig. 1), we loaded 0.25 ng DNA into a 10X Genomics Chromium Controller. The Chromium Controller encapsulates millions of gel beads as GEMs (Gel bead in EMulsion), each of which is loaded with a small number of long DNA molecules. These long molecules are fragmented and ligated with GEM-specific DNA barcodes to generate a 10X library suitable for Illumina sequencing. This library, which we called P50L25, was whole-genome sequenced with 84 million 151 bp-read pairs ( Supplementary Table 1).CO detection using linked-read sequencing 5 After aligning the reads against the Col-0 reference sequence 38 using longranger (v2.2.2, 10X Genomics), we recovered 3.6 million molecules (≥1 kb) including 116 million reads using a newly developed computational tool, DrLink, which can be downloaded at https://github.com/schneebergerlab/DrLink (Fig. 2a; Materials and Methods). On average, these molecules identified by DrLink were ~45 kb in size and were covered by ~21 read pairs, leading to a molecule base coverage of ~0.16x ( Fig. 2b-d; Supplementary Table 1). To avoid chimeras resulting from the accidental co-occurrence of two independent, but closely-spaced molecules with identical barcodes, we selected molecules which were small...

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Genomic and chromatin features shaping meiotic double-strand break formation and repair in mice

Cited by 57 publications

References 109 publications

High-throughput mapping of meiotic crossover and chromosome mis-segregation events in interspecific hybrid mice

High-throughput mapping of meiotic crossover and chromosome mis-segregation events in interspecific hybrid mice

Molecular structures and mechanisms of DNA break processing in mouse meiosis

Linked-read sequencing of gametes allows efficient genome-wide analysis of meiotic recombination

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