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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 | Stefan Krebs | Helmut Blum | Elisabeth Kremmer | Ina M Vorberg | Wolfgang Hammerschmidt | Laurent Lacroix | Olivier Hyrien | Benjamin Audit | Aloys Schepers
eLife | 2021

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.

Pubmed ID: 33683199

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This is a list of tools and resources that we have found mentioned in this publication.


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RRID:SCR_005780

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RRID:SCR_006793

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RRID:SCR_012931

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RRID:SCR_013311

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RRID:AB_2617145

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RRID:SCR_008633

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RRID:SCR_005476

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RRID:SCR_008394

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RRID:SCR_013291

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RRID:SCR_014601

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RRID:SCR_016366

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RRID:CVCL_0511

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RRID:SCR_013035

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