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

Authors: Covadonga Vara, Andreu Paytuví-Gallart, Yasmina Cuartero, Lucía Álvarez-González, Laia Marín-Gual, Francisca Garcia, Beatriu Florit-Sabater, Laia Capilla, Rosa Ana Sanchéz-Guillén, Zaida Sarrate, Riccardo Aiese Cigliano, Walter Sanseverino, Jeremy B. Searle, Jacint Ventura, Marc A. Marti-Renom, François Le Dily & Aurora Ruiz-Herrera

Institutions:

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
Sequentia Biotech, Barcelona, Spain
Centre for Genomic Regulation, The Barcelona Institute for Science and Technology, Barcelona, Spain
CNAG-CRG, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain
Servei de Cultius Cel.lulars, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain
Department of Ecology and Evolutionary Biology, Corson Hall, Cornell University, Ithaca, NY, USA

Publication: Nature Communications

Date: May 2021

Full paper: https://www.nature.com/articles/s41467-021-23270-1

Abstract:

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.