Journal Articles EMBO Journal Year : 2020

Clustering of strong replicators associated with active promoters is sufficient to establish an early-replicating domain

Caroline Brossas
  • Function : Author
Anne-Laure Valton
Sergey V Venev
  • Function : Author
Sabarinadh Chilaka
  • Function : Author
Antonin Counillon
  • Function : Author
Marc Laurent
  • Function : Author
Coralie Goncalves
  • Function : Author
Bénédicte Duriez
Job Dekker
  • Function : Author
Marie-Noëlle Prioleau
  • Function : Author
  • PersonId : 1002275

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 earlyreplicating domains.
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Dates and versions

hal-03023038 , version 1 (25-11-2020)

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Caroline Brossas, Anne-Laure Valton, Sergey V Venev, Sabarinadh Chilaka, Antonin Counillon, et al.. Clustering of strong replicators associated with active promoters is sufficient to establish an early-replicating domain. EMBO Journal, 2020, ⟨10.15252/embj.201899520⟩. ⟨hal-03023038⟩
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