Format

Send to

Choose Destination
Cell Rep. 2019 Jul 9;28(2):352-367.e9. doi: 10.1016/j.celrep.2019.06.037.

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

Author information

1
Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès 08193, Spain; Genome Integrity and Instability Group, Institut de Biotecnologia i Biomedicina (IBB), Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès 08193, Spain.
2
Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès 08193, Spain; Genome Integrity and Instability Group, Institut de Biotecnologia i Biomedicina (IBB), Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès 08193, Spain; Sequentia Biotech, Carrer Comte D'Urgell 240, Barcelona 08036, Spain.
3
Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology (BIST), Carrer del Doctor Aiguader 88, Barcelona 08003, Spain; CNAG-CRG, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 4, Barcelona 08028, Spain.
4
Unitat de Cultius Cel.lulars, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès 08193, Spain.
5
Molecular Mechanisms Program, Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca), Salamanca 37007, Spain.
6
Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology (BIST), Carrer del Doctor Aiguader 88, Barcelona 08003, Spain; Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Carrer del Doctor Aiguader 88, PRBB Building, Barcelona 08003, Spain.
7
CNAG-CRG, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 4, Barcelona 08028, Spain.
8
Sequentia Biotech, Carrer Comte D'Urgell 240, Barcelona 08036, Spain.
9
Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology (BIST), Carrer del Doctor Aiguader 88, Barcelona 08003, Spain; Pompeu Fabra University (UPF), Doctor Aiguader 88, Barcelona 08003, Spain.
10
CNAG-CRG, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 4, Barcelona 08028, Spain; Pompeu Fabra University (UPF), Doctor Aiguader 88, Barcelona 08003, Spain.
11
School of Biotechnology and Biomolecular Sciences, Faculty of Science, UNSW Sydney, NSW 2052, Australia.
12
Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology (BIST), Carrer del Doctor Aiguader 88, Barcelona 08003, Spain; CNAG-CRG, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 4, Barcelona 08028, Spain; Pompeu Fabra University (UPF), Doctor Aiguader 88, Barcelona 08003, Spain; ICREA, Pg. Lluís Companys 23, Barcelona 08010, Spain. Electronic address: martirenom@cnag.crg.eu.
13
Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès 08193, Spain; Genome Integrity and Instability Group, Institut de Biotecnologia i Biomedicina (IBB), Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès 08193, Spain. Electronic address: aurora.ruizherrera@uab.cat.

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.

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center