期刊
CELL REPORTS
卷 28, 期 2, 页码 352-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2019.06.037
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资金
- Ministry of Economy and Competitiveness [BFU2017-89408-R, BFU2013-47736-P, BFU2017-85926-P, CGL2014-54317-P, CGL2017-83802-P]
- Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR) [DI2015, SGR468]
- Spanish Ministry of Economy and Competitiveness [SEV-2012-0208]
- Programa de Apoyo a Planes Estrategicos de Investigacion de Estructuras de Investigacion de Excelencia
- European Regional Development Fund [CLC-2017-01]
- FPI predoctoral fellowship from the Ministry of Economy and Competitiveness [BES-2015-072924]
- Junta de Castilla y Leon [CSI239P18]
- 'Doctorats Industrials' predoctoral fellowship (AGAUR)
- Spanish Institute of Health Carlos III (ISCIII) [CP14/00229]
- Agencia Estatal de Investigacion (AEI)
- FEDER [SAF2017-89109-P]
- European Research Council under the 7th Framework Program FP7/2007-2013 (ERC grant) [609989]
- European Union's Horizon 2020 Research and Innovation Programme [676556]
- MeioNet [BFU2015-71786-REDT]
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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