ALT How vertebrate genomes organize a precise replication timing (RT) program strongly correlated with their organization into A/B compartments has remained unclear. Our results show that clustering of strong origins located at active promoters can 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 RT even when separated by 30 kb • The formation of an early-replicating domain results locally in the formation of a spatial connection between the advanced replicons and in an increase of contacts with active A compartments • The RT of late-replicating domains can be advanced locally by a strong autonomous replicon