Human ORC/MCM density is low in active genes and correlates with replication time but does not delimit initiation zones.
DNA replication initiation
H4K20 methylation
chromosomes
gene expression
human
mouse
ok-seq, chip-seq
orc, mcm complex
replication timing
transcription
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
08 03 2021
08 03 2021
Historique:
received:
16
08
2020
accepted:
05
03
2021
pubmed:
9
3
2021
medline:
10
2
2022
entrez:
8
3
2021
Statut:
epublish
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.
Identifiants
pubmed: 33683199
doi: 10.7554/eLife.62161
pii: 62161
pmc: PMC7993996
doi:
pii:
Substances chimiques
Origin Recognition Complex
0
Minichromosome Maintenance Proteins
EC 3.6.4.12
Banques de données
GEO
['GSE102522', 'GSE116319']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : R01 CA070723
Pays : United States
Informations de copyright
© 2021, Kirstein et al.
Déclaration de conflit d'intérêts
NK, AB, XW, SK, HB, EK, IV, WH, LL, OH, BA, AS No competing interests declared
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