Departament de Biologia Cellular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
Genome Integrity and Instability Group, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
Nat Commun. 2021 May 20;12(1):2981. doi: 10.1038/s41467-021-23270-1.
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.
染色体在核内的空间折叠对基因表达具有调节作用，但基因组重排对这种组织的影响尚不清楚。在这里，我们利用染色质构象捕获技术结合单核苷酸多态性（SNP）基因分型和交叉事件分析，研究了染色体融合如何影响哺乳动物生殖细胞中的高级染色质组织和重组景观。我们证明，染色体融合会在减数分裂过程中改变核结构，包括初级精母细胞中异源相互作用的速率增加，以及染色体联会和轴长的改变。这些拓扑结构的干扰与重组基因组景观的变化有关，导致可检测的基因组足迹。总的来说，我们表明，染色体融合以两种方式影响生殖细胞的动态基因组拓扑结构：（i）改变染色体的核占据和联会，以及（ii）重塑重组景观。
