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Article Dans Une Revue eLife Année : 2021

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

Nina Kirstein
Alexander Buschle
Xia Wu
  • Fonction : Auteur
Stefan Krebs
  • Fonction : Auteur
Helmut Blum
  • Fonction : Auteur
Elisabeth Kremmer
  • Fonction : Auteur
Ina M Vorberg
Wolfgang Hammerschmidt
Laurent Lacroix
  • Fonction : Auteur
Olivier Hyrien
Benjamin L 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. Both, the origin recognition complex (ORC) and the minichromosome maintenance complex (MCM) are significantly 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 regions, 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 specifying when and where replication initiates in human cells.
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Dates et versions

hal-03442948 , version 1 (23-11-2021)

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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 delimit initiation zones. eLife, 2021, 10, ⟨10.7554/elife.62161⟩. ⟨hal-03442948⟩
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