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Genome-wide DNA replication profile for Drosophila melanogaster: a link between transcription and replication timing

Nature Genetics volume 32, pages 438–442 (2002)Cite this article

Abstract

Replication of the genome before mitotic cell division is a highly regulated process that ensures the fidelity of DNA duplication. DNA replication initiates at specific locations, termed origins of replication, and progresses in a defined temporal order during the S phase of the cell cycle. The relationship between replication timing and gene expression has been the subject of some speculation1. A recent genome-wide analysis in Saccharomyces cerevisiae showed no association between replication timing and gene expression2. In higher eukaryotes, the limited number of genomic loci analyzed has not permitted a firm conclusion regarding this association. To explore the relationship between DNA replication and gene expression in higher eukaryotes, we developed a strategy to measure the timing of DNA replication for thousands of genes in a single DNA array hybridization experiment. Using this approach, we generated a genome-wide map of replication timing for Drosophila melanogaster. Moreover, by surveying over 40% of all D. melanogaster genes, we found a strong correlation between DNA replication early in S phase and transcriptional activity. As this correlation does not exist in S. cerevisiae, this interplay between DNA replication and transcription may be a unique characteristic of higher eukaryotes.

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Figure 1: Experimental strategy to measure the timing of DNA replication using spotted microarrays.
Figure 2: Replication timing of genes in the part of chromosome 2L proximal to the telomere.
Figure 3: Replication profile for the sequenced D. melanogaster genome.
Figure 4: Relationship between transcription and timing of DNA replication.

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Acknowledgements

We thank A. Oryan for Kc cells; E. Giniger for coordinating the assembly of the Northwest Fly Consortium microarray; C. Neal for array construction and cDNA analysis; J. Schreiber, D. Cimbora and members of the Groudine lab for suggestions; and S. Henikoff, D. Gottschling and M. Lorincz for comments on the manuscript. This work was supported in part by US National Institute of Health grants to M.G. and C.K., a grant from the Netherlands Academy of Sciences to B.v.S. and a fellowship grant from the Rett Syndrome Research Foundation to D.S.

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Authors and Affiliations

  1. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, 98109, Washington, USA

    Dirk Schübeler, David Scalzo & Mark Groudine

  2. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, 98109, Washington, USA

    Charles Kooperberg

  3. Netherlands Cancer Institute, Amsterdam, The Netherlands

    Bas van Steensel

  4. DNA array facility, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Jeffrey Delrow

  5. Department of Radiation Oncology, University of Washington, Seattle, Washington, USA

    Mark Groudine

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  1. Dirk Schübeler
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Correspondence to Dirk Schübeler or Mark Groudine.

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Schübeler, D., Scalzo, D., Kooperberg, C. et al. Genome-wide DNA replication profile for Drosophila melanogaster: a link between transcription and replication timing. Nat Genet 32, 438–442 (2002). https://doi.org/10.1038/ng1005

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