Clustering of strong replicators associated with active promoters is sufficient to establish an early-replicating domain
Authors
Brossas, CarolineValton, Anne-Laure
Venev, Sergey V.
Chilaka, Sabarinadh
Counillon, Antonin
Laurent, Marc
Goncalves, Coralie
Duriez, Benedicte
Picard, Franck
Dekker, Job
Prioleau, Marie-Noelle
UMass Chan Affiliations
Program in Systems BiologyDepartment of Biochemistry and Molecular Pharmacology
Document Type
Journal ArticlePublication Date
2020-11-02Keywords
chromatin accessibilitynuclear organization
promoter
replication origin
replication timing
Biochemistry, Biophysics, and Structural Biology
Genetics and Genomics
Systems Biology
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Show full item recordAbstract
Vertebrate genomes replicate according to a precise temporal program strongly correlated with their organization into A/B compartments. Until now, the molecular mechanisms underlying the establishment of early-replicating domains remain largely unknown. We defined two minimal cis-element modules containing a strong replication origin and chromatin modifier binding sites capable of shifting a targeted mid-late-replicating region for earlier replication. The two origins overlap with a constitutive or a silent tissue-specific promoter. When inserted side-by-side, these modules advance replication timing over a 250 kb region through the cooperation with one endogenous origin located 30 kb away. Moreover, when inserted at two chromosomal sites separated by 30 kb, these two modules come into close physical proximity and form an early-replicating domain establishing more contacts with active A compartments. The synergy depends on the presence of the active promoter/origin. Our results show that clustering of strong origins located at active promoters can establish early-replicating domains.Source
Brossas C, Valton AL, Venev SV, Chilaka S, Counillon A, Laurent M, Goncalves C, Duriez B, Picard F, Dekker J, Prioleau MN. Clustering of strong replicators associated with active promoters is sufficient to establish an early-replicating domain. EMBO J. 2020 Nov 2;39(21):e99520. doi: 10.15252/embj.201899520. Epub 2020 Sep 16. PMID: 32935369; PMCID: PMC7604622. Link to article on publisher's site
DOI
10.15252/embj.201899520Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41665PubMed ID
32935369Related Resources
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Copyright 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license.Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.15252/embj.201899520
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Except where otherwise noted, this item's license is described as Copyright 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license.