3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells.

In mammalian cells, chromosomal replication starts at thousands of origins at which replisomes are assembled. Replicative stress triggers additional initiation events from 'dormant' origins whose genomic distribution and regulation are not well understood. In this study, we have analyzed o...

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Autores: Jodkowska, Karolina, Pancaldi, Vera, Rigau, Maria, Almeida, Ricardo, Fernández-Justel, José M, Graña-Castro, Osvaldo, Rodríguez-Acebes, Sara, Rubio-Camarillo, Miriam, Carrillo-de-Santa-Pau, Enrique, Pisano, David, Al-Shahrour, Fatima, Valencia, Alfonso, Gómez, María, Méndez, Juan
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/18932
Acceso en línea:http://hdl.handle.net/20.500.12105/18932
Access Level:acceso abierto
Palabra clave:Replication Origin
Chromatin
Animals
Mice
Mouse Embryonic Stem Cells
DNA Replication
Cell Cycle Proteins
Mammals
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spelling 3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells.Jodkowska, KarolinaPancaldi, VeraRigau, MariaAlmeida, RicardoFernández-Justel, José MGraña-Castro, OsvaldoRodríguez-Acebes, SaraRubio-Camarillo, MiriamCarrillo-de-Santa-Pau, EnriquePisano, DavidAl-Shahrour, FatimaValencia, AlfonsoGómez, MaríaMéndez, JuanReplication OriginChromatinAnimalsMiceMouse Embryonic Stem CellsDNA ReplicationCell Cycle ProteinsMammalsIn mammalian cells, chromosomal replication starts at thousands of origins at which replisomes are assembled. Replicative stress triggers additional initiation events from 'dormant' origins whose genomic distribution and regulation are not well understood. In this study, we have analyzed origin activity in mouse embryonic stem cells in the absence or presence of mild replicative stress induced by aphidicolin, a DNA polymerase inhibitor, or by deregulation of origin licensing factor CDC6. In both cases, we observe that the majority of stress-responsive origins are also active in a small fraction of the cell population in a normal S phase, and stress increases their frequency of activation. In a search for the molecular determinants of origin efficiency, we compared the genetic and epigenetic features of origins displaying different levels of activation, and integrated their genomic positions in three-dimensional chromatin interaction networks derived from high-depth Hi-C and promoter-capture Hi-C data. We report that origin efficiency is directly proportional to the proximity to transcriptional start sites and to the number of contacts established between origin-containing chromatin fragments, supporting the organization of origins in higher-level DNA replication factories.Oxford University PressMinisterio de Ciencia y Tecnología (España)Fundação para a Ciência e Tecnologia (Portugal)Fundación La CaixaUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Foundation for Polish Science20242024-03-1320222022-11-2820222022-11-28journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articlehttp://hdl.handle.net/20.500.12105/18932reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/189322026-06-12T12:43:37Z
dc.title.none.fl_str_mv 3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells.
title 3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells.
spellingShingle 3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells.
Jodkowska, Karolina
Replication Origin
Chromatin
Animals
Mice
Mouse Embryonic Stem Cells
DNA Replication
Cell Cycle Proteins
Mammals
title_short 3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells.
title_full 3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells.
title_fullStr 3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells.
title_full_unstemmed 3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells.
title_sort 3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells.
dc.creator.none.fl_str_mv Jodkowska, Karolina
Pancaldi, Vera
Rigau, Maria
Almeida, Ricardo
Fernández-Justel, José M
Graña-Castro, Osvaldo
Rodríguez-Acebes, Sara
Rubio-Camarillo, Miriam
Carrillo-de-Santa-Pau, Enrique
Pisano, David
Al-Shahrour, Fatima
Valencia, Alfonso
Gómez, María
Méndez, Juan
author Jodkowska, Karolina
author_facet Jodkowska, Karolina
Pancaldi, Vera
Rigau, Maria
Almeida, Ricardo
Fernández-Justel, José M
Graña-Castro, Osvaldo
Rodríguez-Acebes, Sara
Rubio-Camarillo, Miriam
Carrillo-de-Santa-Pau, Enrique
Pisano, David
Al-Shahrour, Fatima
Valencia, Alfonso
Gómez, María
Méndez, Juan
author_role author
author2 Pancaldi, Vera
Rigau, Maria
Almeida, Ricardo
Fernández-Justel, José M
Graña-Castro, Osvaldo
Rodríguez-Acebes, Sara
Rubio-Camarillo, Miriam
Carrillo-de-Santa-Pau, Enrique
Pisano, David
Al-Shahrour, Fatima
Valencia, Alfonso
Gómez, María
Méndez, Juan
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia y Tecnología (España)
Fundação para a Ciência e Tecnologia (Portugal)
Fundación La Caixa
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Foundation for Polish Science
dc.subject.none.fl_str_mv Replication Origin
Chromatin
Animals
Mice
Mouse Embryonic Stem Cells
DNA Replication
Cell Cycle Proteins
Mammals
topic Replication Origin
Chromatin
Animals
Mice
Mouse Embryonic Stem Cells
DNA Replication
Cell Cycle Proteins
Mammals
description In mammalian cells, chromosomal replication starts at thousands of origins at which replisomes are assembled. Replicative stress triggers additional initiation events from 'dormant' origins whose genomic distribution and regulation are not well understood. In this study, we have analyzed origin activity in mouse embryonic stem cells in the absence or presence of mild replicative stress induced by aphidicolin, a DNA polymerase inhibitor, or by deregulation of origin licensing factor CDC6. In both cases, we observe that the majority of stress-responsive origins are also active in a small fraction of the cell population in a normal S phase, and stress increases their frequency of activation. In a search for the molecular determinants of origin efficiency, we compared the genetic and epigenetic features of origins displaying different levels of activation, and integrated their genomic positions in three-dimensional chromatin interaction networks derived from high-depth Hi-C and promoter-capture Hi-C data. We report that origin efficiency is directly proportional to the proximity to transcriptional start sites and to the number of contacts established between origin-containing chromatin fragments, supporting the organization of origins in higher-level DNA replication factories.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-11-28
2022
2022-11-28
2024
2024-03-13
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/18932
url http://hdl.handle.net/20.500.12105/18932
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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