Genome-wide sequence and functional analysis of early replicating DNA in normal human fibroblasts Public Deposited

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  • Kaufman, David
    • Affiliation: School of Medicine, Department of Pathology and Laboratory Medicine
  • Cohen, Stephanie M
    • Affiliation: School of Medicine, Department of Pathology and Laboratory Medicine
  • Doggett, Norman A
    • Other Affiliation: Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
  • Furey, Terrence S
    • Other Affiliation: Institute for Genome Sciences and Policy, Duke University, Durham, NC, 27708, USA
  • Abstract Background The replication of mammalian genomic DNA during the S phase is a highly coordinated process that occurs in a programmed manner. Recent studies have begun to elucidate the pattern of replication timing on a genomic scale. Using a combination of experimental and computational techniques, we identified a genome-wide set of the earliest replicating sequences. This was accomplished by first creating a cosmid library containing DNA enriched in sequences that replicate early in the S phase of normal human fibroblasts. Clone ends were then sequenced and aligned to the human genome. Results By clustering adjacent or overlapping early replicating clones, we identified 1759 "islands" averaging 100 kb in length, allowing us to perform the most detailed analysis to date of DNA characteristics and genes contained within early replicating DNA. Islands are enriched in open chromatin, transcription related elements, and Alu repetitive elements, with an underrepresentation of LINE elements. In addition, we found a paucity of LTR retroposons, DNA transposon sequences, and an enrichment in all classes of tandem repeats, except for dinucleotides. Conclusion An analysis of genes associated with islands revealed that nearly half of all genes in the WNT family, and a number of genes in the base excision repair pathway, including four of ten DNA glycosylases, were associated with island sequences. Also, we found an overrepresentation of members of apoptosis-associated genes in very early replicating sequences from both fibroblast and lymphoblastoid cells. These data suggest that there is a temporal pattern of replication for some functionally related genes.
Date of publication
  • doi:10.1186/1471-2164-7-301
  • 17134498
Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Stephanie M Cohen et al.; licensee BioMed Central Ltd.
Journal title
  • BMC Genomics
Journal volume
  • 7
Journal issue
  • 1
Page start
  • 301
  • English
Is the article or chapter peer-reviewed?
  • Yes
  • 1471-2164
Bibliographic citation
  • BMC Genomics. 2006 Nov 29;7(1):301
  • Open Access
  • BioMed Central Ltd

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