Título:
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Three-dimensional genomic structure and cohesin occupancy correlate with transcriptional activity during spermatogenesis
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Autor/a:
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Vara, Covadonga; Paytuví Gallart, Andreu; Cuartero, Yasmina; Le Dily, François; Garcia, Francisca; Salvà-Castro, Judit; Gómez-H, Laura; Julià, Eva; Moutinho, Catia; Aiese Cigliano, Riccardo; Sanseverino, Walter; Fornas Carreño, Oscar; Pendás, Alberto M.; Heyn, Holger; Waters, Paul D.; Marti-Renom, Marc A.; Ruiz Herrera, Aurora
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Abstract:
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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. |
Abstract:
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This work was supported by the Ministry of Economy and Competitiveness (BFU2017-89408-R to A.M.P.; BFU2013-47736-P and BFU2017-85926-P to M.A.M.-R.; and CGL2014-54317-P and CGL2017-83802-P to A.R.-H.) and the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) (DI2015 to A.R.-H. and R.A.C., as well as SGR468 to M.A.M-R.). Work at CRG, BIST, and UPF was in part funded by the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013-2017’ (SEV-2012-0208), and ‘Centro de Excelencia María de Maeztu 2016-2019.’ CIC-IBMCC is supported by the Programa de Apoyo a Planes Estratégicos de Investigación de Estructuras de Investigación de Excelencia, co-funded by Junta de Castilla y León (CSI239P18) and the European Regional Development Fund (CLC–2017–01). C.V. is supported by a FPI predoctoral fellowship from the Ministry of Economy and Competitiveness (BES-2015-072924). 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), the Agencia Estatal de Investigación (AEI), and FEDER (SAF2017-89109-P). C.M. is an Asociación Española Contra el Cáncer (AECC) postdoctoral fellow. M.A.M.-R. acknowledges support by the European Research Council under the 7th Framework Program FP7/2007-2013 (ERC grant agreement 609989) and the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement 676556). A.M.P. and A.R.-H. also acknowledge support from MeioNet (BFU2015-71786-REDT). |
Derechos:
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© 2019 The Author(s).This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
http://creativecommons.org/licenses/by/4.0/ |
Tipo de documento:
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Artículo Artículo - Versión publicada |
Editor:
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Elsevier
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