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Página principal > Artículos > Artículos publicados > Three-dimensional genomic structure and cohesin occupancy correlate with transcriptional activity during spermatogenesis |
Fecha: | 2019 |
Resumen: | 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. |
Ayudas: | European Commission 676556 European Commission 609989 Ministerio de Economía y Competitividad BFU2017-89408-R Ministerio de Economía y Competitividad BFU2017-85926-P Ministerio de Economía y Competitividad CGL2017-83802-P Ministerio de Economía y Competitividad SAF2017-89109-P Ministerio de Economía y Competitividad BES-2015-072924 Ministerio de Economía y Competitividad BFU2015-71786-REDT Ministerio de Economía y Competitividad CGL2014-54317-P Ministerio de Economía y Competitividad BFU2013-47736-P Ministerio de Economía y Competitividad SEV-2012-0208 Agència de Gestió d'Ajuts Universitaris i de Recerca DI2015 |
Nota: | Altres ajuts: Agaur SGR468 to M.A.M-R. A.P.-G. is supported by a 'Doctorats Industrials' predoctoral fellowship (AGAUR). H.H. is a Miguel Servet (CP14/00229) researcher funded by the Spanish Institute of Health Carlos III (ISCIII) |
Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Publicado en: | Cell reports, Vol. 28, issue 2 (Jul. 2019) , p. 352-367, ISSN 2211-1247 |
26 p, 7.4 MB |