Abstract
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.
Dokumententyp: | Zeitschriftenartikel |
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Fakultät: | Chemie und Pharmazie > Department Biochemie |
Themengebiete: | 500 Naturwissenschaften und Mathematik > 540 Chemie |
URN: | urn:nbn:de:bvb:19-epub-99559-5 |
ISSN: | 2050-084X |
Sprache: | Englisch |
Dokumenten ID: | 99559 |
Datum der Veröffentlichung auf Open Access LMU: | 05. Jun. 2023, 15:32 |
Letzte Änderungen: | 20. Okt. 2023, 17:50 |