Journal article
Transcription initiation activity sets replication origin efficiency in mammalian cells.
- Abstract:
- Genomic mapping of DNA replication origins (ORIs) in mammals provides a powerful means for understanding the regulatory complexity of our genome. Here we combine a genome-wide approach to identify preferential sites of DNA replication initiation at 0.4% of the mouse genome with detailed molecular analysis at distinct classes of ORIs according to their location relative to the genes. Our study reveals that 85% of the replication initiation sites in mouse embryonic stem (ES) cells are associated with transcriptional units. Nearly half of the identified ORIs map at promoter regions and, interestingly, ORI density strongly correlates with promoter density, reflecting the coordinated organisation of replication and transcription in the mouse genome. Detailed analysis of ORI activity showed that CpG island promoter-ORIs are the most efficient ORIs in ES cells and both ORI specification and firing efficiency are maintained across cell types. Remarkably, the distribution of replication initiation sites at promoter-ORIs exactly parallels that of transcription start sites (TSS), suggesting a co-evolution of the regulatory regions driving replication and transcription. Moreover, we found that promoter-ORIs are significantly enriched in CAGE tags derived from early embryos relative to all promoters. This association implies that transcription initiation early in development sets the probability of ORI activation, unveiling a new hallmark in ORI efficiency regulation in mammalian cells.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.5MB, Terms of use)
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- Publisher copy:
- 10.1371/journal.pgen.1000446
Authors
- Publisher:
- Public Library of Science
- Journal:
- PLoS genetics More from this journal
- Volume:
- 5
- Issue:
- 4
- Pages:
- e1000446
- Publication date:
- 2009-04-01
- DOI:
- EISSN:
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1553-7404
- ISSN:
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1553-7390
- Language:
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English
- Keywords:
- UUID:
-
uuid:eeed55a8-5a1a-4bf1-ac8d-2ec3cc6fc8af
- Local pid:
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pubs:100076
- Source identifiers:
-
100076
- Deposit date:
-
2012-12-19
Terms of use
- Copyright holder:
- Sequeira-Mendes et al
- Copyright date:
- 2009
- Notes:
- Copyright 2009 Sequeira-Mendes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Licence:
- CC Attribution (CC BY)
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