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

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

Research output: Contribution to journalArticleResearch

24 Citations (Scopus)

Abstract

© 2019 The Author(s) 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. The formation of mammalian germ cells involves dramatic chromosomal movements and chromatin remodeling, whose regulatory pathways are far from understood. Vara et al. show how the dynamics of insulator proteins’ occupancy and transcriptional activity are coupled during the 3D genome re-organization that takes place during mouse spermatogenesis.
Original languageEnglish
Pages (from-to)352-367.e9
JournalCell Reports
Volume28
DOIs
Publication statusPublished - 9 Jul 2019

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