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.

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