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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)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Chromosomes ; Gene Expression ; Human ; Mouse
ISSN (print) / ISBN 2050-084X
e-ISSN 2050-084X
Zeitschrift eLife
Quellenangaben Band: 10, Heft: , Seiten: , Artikelnummer: e62161 Supplement: ,
Verlag eLife Sciences Publications
Verlagsort Sheraton House, Castle Park, Cambridge, Cb3 0ax, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CF Monoclonal Antibodies (CF-MAB)
Research Unit Gene Vector (AGV)
Förderungen 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