Initiation of DNA replication at CpG islands in mammalian chromosomes.
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.
Delgado
S
S
Instituto de Microbiología Bioquímica, CSIC/Universidad de Salamanca, Edificio Departamental, Campus Miguel de Unamuno, 37007-Salamanca, Spain.
Gómez
M
M
Bird
A
A
Antequera
F
F
D000228:Adenine Phosphoribosyltransferase / Q000235:genetics; D000818:Animals; D016466:CHO Cells; D002875:Chromosomes; D018899:CpG Islands; D006224:Cricetinae; D004261:DNA Replication; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D008322:Mammals; D016133:Polymerase Chain Reaction; D018741:Replication Origin; D016196:S Phase; D013937:Thymidine Kinase / Q000235:genetics; D014407:Tumor Cells, Cultured
D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; C077214:L1Hs-encoded protein p40, human; D000228:Adenine Phosphoribosyltransferase; D013937:Thymidine Kinase