Initiation of DNA replication at CpG islands in mammalian chromosomes
Open accessAbstract
CpG islands are G+C-rich regions approximately 1 kb long that are free of methylation and contain the promoters of many mammalian genes. Analysis of in vivo replication intermediates at three hamster genes and one human gene showed that the CpG island regions, but not their flanks, were present in very short nascent strands, suggesting that they are replication origins (ORIs). CpG island-like fragments were enriched in a population of short nascent strands from human erythroleukaemic cells, suggesting that islands constitute a significant fraction of endogenous ORIs. Correspondingly, bulk CpG islands were found to replicate coordinately early in S phase. Our results imply that CpG islands are initiation sites for both transcription and DNA replication, and may represent genomic footprints of replication initiation.
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It may be an impossible task to completely eliminate promoter activity since CGI, TSS, and origins of replication are often associated together.
“Unfortunately, it may be an impossible task to completely eliminate promoter activity since CGI, TSS, and origins of replication are often associated together.31”
From Adeno-Associated Virus Serotype-Specific Inverted Terminal Repeat Sequence Role in Vector Transgene Expression (2020) · cites this paper as [31]
The Introduction (page unavailable) says CpG islands are associated with gene promoters and that the studied island regions initiate both transcription and DNA replication. The “DNA replication and gene transcription” section (page unavailable) likewise describes co-localisation of CpG islands and replication origins. The paper does not assess whether promoter activity can be completely eliminated, so it supports the association but not the suggested difficulty of elimination. (LLM, conf=0.85)
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Bird, A. (2002) · Genes & Development · doi:10.1101/gad.947102 · Cited by 7,124 · see citing works
Self-citationCpG islands and the regulation of transcription
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Self-citationBrock, G. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.6.1061 · Cited by 122 · see citing works
Earley, L. F., Conatser, L. M., Lue, V. M., Dobbins, A. L., Li, C., Hirsch, M. L., & Samulski, R. J. (2020) · Human Gene Therapy · doi:10.1089/hum.2019.274 · Cited by 116 · see citing works
- Authors
- Delgado, S., Gómez, M., Bird, A., & Antequera, F.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- University of Edinburgh (GB)
- Corresponding author
- Antequera, Francisco
- Venue
- The EMBO Journal
- Published
- 1998-04-15
- Volume
- 17
- Issue
- 8
- Pages
- 2426-2435
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1170585
- OpenAlex
- W2127779731
- Cited by
- 242
- References
- 0
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 1 · 2023: 5 · 2022: 2 · 2021: 1 · 2020: 7 · 2019: 9 · 2018: 8 · 2017: 5 · 2016: 10 · 2015: 9 · 2014: 6 · 2013: 6 · 2012: 9
- FWCI
- 5.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- Israel Cancer Research Fund
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- CpG islands, DNA replication initiation, origin of replication, replication intermediates, DNA methylation, transcription initiation, S phase
- MeSH terms
- Adenine Phosphoribosyltransferase, Animals, Chromosomes, DNA Transposable Elements, DNA Replication, DNA-Binding Proteins, Cricetinae, Humans, Mammals, Thymidine Kinase, Tumor Cells, Cultured, Polymerase Chain Reaction, S Phase, CHO Cells, Replication Origin, CpG Islands
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