|Title||Three-Dimensional Genomic Structure and Cohesin Occupancy Correlate with Transcriptional Activity during Spermatogenesis.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Vara, C, Paytuví-Gallart, A, Cuartero, Y, Le Dily, F, Garcia, F, Salvà-Castro, J, Gómez-H, L, Julià, E, Moutinho, C, Cigliano, RAiese, Sanseverino, W, Fornas, O, Pendás, AM, Heyn, H, Waters, PD, Marti-Renom, MA, Ruiz-Herrera, A|
|Date Published||2019 Jul 09|
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.
|Alternate Journal||Cell Rep|
|PubMed Central ID||PMC6635386|