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Kirstein, N. ; Buschle, A. ; Wu, X.* ; Krebs, S.* ; Blum, H.* ; Kremmer, E. ; Vorberg, I.M.* ; Hammerschmidt, W. ; Lacroix, L.* ; Hyrien, O.* ; Audit, B.* ; Schepers, A.

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

eLife 10:e62161 (2021)

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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 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 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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Chromosomes ; Gene Expression ; Human ; Mouse

ISSN (print) / ISBN 2050-084X

e-ISSN 2050-084X

Journal eLife

Quellenangaben Volume: 10, Article Number: e62161

Publisher eLife Sciences Publications

Publishing Place Sheraton House, Castle Park, Cambridge, Cb3 0ax, England

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) CF Monoclonal Antibodies (CF-MAB)
Research Unit Gene Vector (AGV)

Grants Association pour la Recherche sur le Cancer
Ligue Nationale Contre le Cancer
Canceropole Ile-de-France
NCI NIH HHS
Deutsche Forschungsgemeinschaft
Agence Nationale de la Recherche
Fondation pour la Recherche Medicale