Clustering of strong replicators associated with active promoters is sufficient to establish an early‐replicating domain. (16th September 2020)

• Record Type: Journal Article
• Authors: Brossas, Caroline; Valton, Anne‐Laure; Venev, Sergey V; Chilaka, Sabarinadh; Counillon, Antonin; Laurent, Marc; Goncalves, Coralie; Duriez, Bénédicte; Picard, Franck; Dekker, Job; Prioleau, Marie‐Noëlle
• Is Part Of: EMBO journal. Volume 39:Number 21(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-09-16
• Subjects: chromatin accessibility -- nuclear organization -- promoter -- replication origin -- replication timing; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.201899520
• Languages: English
• ISSNs: 0261-4189

Abstract

Abstract: 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. Synopsis: How vertebrate genomes organize a precise replication timing program that is strongly correlated with their organization into so‐called A/B compartments has remained unclear. Here, clustering of strong origins located at active promoters is shown to be able to establish early‐replicating domains. Two replicators carrying timing information can act in cooperation if located in close proximity. Strong autonomous replicons overlapping an active promoter can act in synergy on replication timing even when separated by 30 kb. Formation of an early‐replicating domain results locally in formation of a spatial connection between advanced replicons, and in an increase of contacts to active A compartments. Replication timing of late‐replicating domains can be advanced locally by a strong autonomous replicon. Abstract : Two replicators carrying timing information can cooperate when located in proximity, and advance replication timing by forming higher‐order chromatin contacts with active "A" compartments.