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Initiation of DNA replication at CpG islands in mammalian chromosomes
Author(s) -
Delgado Sonia,
Gómez María,
Bird Adrian,
Antequera Francisco
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.8.2426
Subject(s) - biology , cpg site , dna replication , dna methylation , replication timing , genetics , control of chromosome duplication , pre replication complex , gene , dna , methylation , origin recognition complex , microbiology and biotechnology , eukaryotic dna replication , gene expression
CpG islands are G+C‐rich regions ∼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.