The impact of chromosomal fusions on 3D genome folding and recombination in the germ line

Author:

Vara CovadongaORCID,Paytuví-Gallart AndreuORCID,Cuartero Yasmina,Álvarez-González Lucía,Marín-Gual LaiaORCID,Garcia Francisca,Florit-Sabater Beatriu,Capilla Laia,Sanchéz-Guillén Rosa Ana,Sarrate ZaidaORCID,Aiese Cigliano Riccardo,Sanseverino WalterORCID,Searle Jeremy B.,Ventura Jacint,Marti-Renom Marc A.ORCID,Le Dily FrançoisORCID,Ruiz-Herrera AuroraORCID

Abstract

AbstractThe 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.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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