期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-23270-1
关键词
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资金
- Ministry of Economy and Competitiveness [CGL2014-54317-P, CGL2017-83802-P, BFU2013-47736-P, BFU2017-85926-P, CGL2010-15243, BES-2015-072924, PRE-2018-083257]
- Agencia de Gestio d'Ajuts Universitaris i de Recerca, AGAUR [DI2015, SGR1215, SGR468]
- Ministry of Science, Innovation and University [FPU18/03867]
- European Research Council under the 7th Framework Program FP7/2007-2013 (ERC) [609989]
- European Union's Horizon 2020 research and innovation program [676556]
- MeioNet [BFU2015-71786-REDT]
The study investigates the impact of chromosomal fusions on the higher-order chromatin organization and recombination landscapes in mammalian germ cells. Results show that chromosomal fusions alter the nuclear architecture during meiosis, affecting heterologous interactions and chromosome synapsis. These disturbances in topology also reshape landscapes of recombination, indicating a significant impact on genome function and fertility.
The spatial folding of chromosomes inside the nucleus has regulatory effects on gene expression, yet the impact of genome reshuffling on this organization remains unclear. Here, we take advantage of chromosome conformation capture in combination with single-nucleotide polymorphism (SNP) genotyping and analysis of crossover events to study how the higher-order chromatin organization and recombination landscapes are affected by chromosomal fusions in the mammalian germ line. We demonstrate that chromosomal fusions alter the nuclear architecture during meiosis, including an increased rate of heterologous interactions in primary spermatocytes, and alterations in both chromosome synapsis and axis length. These disturbances in topology were associated with changes in genomic landscapes of recombination, resulting in detectable genomic footprints. Overall, we show that chromosomal fusions impact the dynamic genome topology of germ cells in two ways: (i) altering chromosomal nuclear occupancy and synapsis, and (ii) reshaping landscapes of recombination. How mammalian genomes are packaged and the heritability of structural variations in genome folding is incomplete. Here, the authors investigate the impact of chromosomal fusions on three-dimensional genome topology and meiotic recombination, highlighting the implications of large-scale genome reorganizations on genome function, evolution, and fertility.
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