Department of Biochemistry and Molecular Pharmacology; Program in Systems Biology
Biochemistry, Biophysics, and Structural Biology | Genetics and Genomics | Systems Biology
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.
chromatin accessibility, nuclear organization, promoter, replication origin, replication timing
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DOI of Published Version
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
The EMBO journal
Brossas C, Valton A, Venev SV, Chilaka S, Counillon A, Laurent M, Goncalves C, Duriez B, Picard F, Dekker J, Prioleau M. (2020). Clustering of strong replicators associated with active promoters is sufficient to establish an early-replicating domain. Open Access Publications by UMMS Authors. https://doi.org/10.15252/embj.201899520. Retrieved from https://escholarship.umassmed.edu/oapubs/4456
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