Three-Dimensional Genomic Structure and Cohesin Occupancy Correlate with Transcriptional Activity during Spermatogenesis

Authors: Covadonga Vara, Andreu Paytuví-Gallart, Yasmina Cuartero, François Le Dily, Francisca Garcia, Judit Salvà-Castro, Laura Gómez-H, Eva Julià, Catia Moutinho, Riccardo Aiese Cigliano, Walter Sanseverino, Oscar Fornas, Alberto M. Pendás, Holger Heyn, Paul D. Waters, Marc A. Marti-Renom, Aurora Ruiz-Herrera

Institutions:

Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès 08193, Spain
Sequentia Biotech, Carrer Comte D’Urgell 240, Barcelona 08036, Spain
Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology (BIST), Carrer del Doctor Aiguader 88, Barcelona 08003, Spain
Unitat de Cultius Cel.lulars, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès 08193, Spain
Molecular Mechanisms Program, Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca), Salamanca 37007, Spain
CNAG-CRG, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 4, Barcelona 08028, Spain
School of Biotechnology and Biomolecular Sciences, Faculty of Science, UNSW Sydney, NSW 2052, Australia

Publication: Cell Reports

Date: July 2019

Full paper: https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30803-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124719308034%3Fshowall%3Dtrue#%20

Abstract:

Mammalian gametogenesis involves dramatic and tightly regulated chromatin remodeling, whose regulatory pathways remain largely unexplored. Here, we generate a comprehensive high-resolution structural and functional atlas of mouse spermatogenesis by combining in situ chromosome conformation capture sequencing (Hi-C), RNA sequencing (RNA-seq), and chromatin immunoprecipitation sequencing (ChIP-seq) of CCCTC-binding factor (CTCF) and meiotic cohesins, coupled with confocal and super-resolution microscopy. Spermatogonia presents well-defined compartment patterns and topological domains. However, chromosome occupancy and compartmentalization are highly re-arranged during prophase I, with cohesins bound to active promoters in DNA loops out of the chromosomal axes. Compartment patterns re-emerge in round spermatids, where cohesin occupancy correlates with transcriptional activity of key developmental genes. The compact sperm genome contains compartments with actively transcribed genes but no fine-scale topological domains, concomitant with the presence of protamines. Overall, we demonstrate how genome-wide cohesin occupancy and transcriptional activity is associated with three-dimensional (3D) remodeling during spermatogenesis, ultimately reprogramming the genome for the next generation.