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

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cris.lastimport.scopus2024-02-12T19:39:55Z
dc.abstract.enIn 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.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorJodkowska, Karolina
dc.contributor.authorMéndez, Juan
dc.contributor.authorGómez, María
dc.contributor.authorValencia, Alfonso
dc.contributor.authorAl-Shahrour, Fátima
dc.contributor.authorPisano, David
dc.contributor.authorCarrillo-de Santa Pau, Enrique
dc.contributor.authorRubio-Camarillo, Miriam
dc.contributor.authorRodríguez-Acebes, Sara
dc.contributor.authorGraña-Castro, Osvaldo
dc.contributor.authorFernández-Justel, José M
dc.contributor.authorAlmeida, Ricardo
dc.contributor.authorRigau, Maria
dc.contributor.authorPancaldi, Vera
dc.date.accessioned2024-01-24T15:35:54Z
dc.date.available2024-01-24T15:35:54Z
dc.date.issued2022
dc.description.financePublikacja bezkosztowa
dc.description.number21
dc.description.volume50
dc.identifier.doi10.1093/NAR/GKAC1111
dc.identifier.issn0305-1048
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/100060
dc.identifier.weblinkhttps://academic.oup.com/nar/article-pdf/50/21/12149/47999088/gkac1111.pdf
dc.languageeng
dc.pbn.affiliationbiological sciences
dc.relation.ispartofNucleic Acids Research
dc.relation.pages12149-12165
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.title3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells
dc.typeJournalArticle
dspace.entity.typePublication