Human ORC/MCM density is low in active genes and correlates with replication time but does not solely define replication initiation zones - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Pré-Publication, Document De Travail Année : 2020

Human ORC/MCM density is low in active genes and correlates with replication time but does not solely define replication initiation zones

Nina Kirstein
Alexander Buschle
Xia Wu
  • Fonction : Auteur
Stefan Krebs
  • Fonction : Auteur
Helmut Blum
  • Fonction : Auteur
Wolfgang Hammerschmidt
Laurent Lacroix
  • Fonction : Auteur
Olivier Hyrien
Benjamin Audit
Aloys Schepers

Résumé

Eukaryotic DNA replication initiates during S phase from origins that have been licensed in the preceding G1 phase. Here, we compare ChIP-seq profiles of the licensing factors Orc2, Orc3, Mcm3, and Mcm7 with gene expression, replication timing and fork directionality profiles obtained by RNA-seq, Repli-seq and OK-seq. ORC and MCM are strongly and homogeneously depleted from transcribed genes, enriched at gene promoters, and more abundant in early-than in late-replicating domains. Surprisingly, after controlling these variables, no difference in ORC/MCM density is detected between initiation zones, termination zones, unidirectionally replicating and randomly replicating regions. Therefore, ORC/MCM density correlates with replication timing but does not solely regulate the probability of replication initiation. Interestingly, H4K20me3, a histone modification proposed to facilitate late origin licensing, was enriched in late replicating initiation zones and gene deserts of stochastic replication fork direction. We discuss potential mechanisms that specify when and where replication initiates in human cells.

Dates et versions

hal-03052952 , version 1 (10-12-2020)

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Citer

Nina Kirstein, Alexander Buschle, Xia Wu, Stefan Krebs, Helmut Blum, et al.. Human ORC/MCM density is low in active genes and correlates with replication time but does not solely define replication initiation zones. 2020. ⟨hal-03052952⟩

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