Genome-wide identification and characterization of replication origins by deep sequencing
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gb-2012-13-4-r27.pdf
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Author(s)
Xu, Jia
Yanagisawa, Yoshimi
Tsankov, Alexander M
Hart, Christopher
Aoki, Keita
Kommajosyula, Naveen
Steinmann, Kathleen E.
Bochicchio, James
Russ, Carsten
Regev, Aviv
Date Issued
April 2012
Journal
Genome Biology
Publisher
Springer (Biomed Central Ltd.)
Citation
Xu, Jia et al. “Genome-wide Identification and Characterization of Replication Origins by Deep Sequencing.” Genome Biology 13.4 (2012): R27. Web. 25 May 2012.
Version
Final published version
Abstract
Background
DNA replication initiates at distinct origins in eukaryotic genomes, but the genomic features that define these sites are not well understood.
Results
We have taken a combined experimental and bioinformatic approach to identify and characterize origins of replication in three distantly related fission yeasts: Schizosaccharomyces pombe, Schizosaccharomyces octosporus and Schizosaccharomyces japonicus. Using single-molecule deep sequencing to construct amplification-free high-resolution replication profiles, we located origins and identified sequence motifs that predict origin function. We then mapped nucleosome occupancy by deep sequencing of mononucleosomal DNA from the corresponding species, finding that origins tend to occupy nucleosome-depleted regions.
Conclusions
The sequences that specify origins are evolutionarily plastic, with low complexity nucleosome-excluding sequences functioning in S. pombe and S. octosporus, and binding sites for trans-acting nucleosome-excluding proteins functioning in S. japonicus. Furthermore, chromosome-scale variation in replication timing is conserved independently of origin location and via a mechanism distinct from known heterochromatic effects on origin function. These results are consistent with a model in which origins are simply the nucleosome-depleted regions of the genome with the highest affinity for the origin recognition complex. This approach provides a general strategy for understanding the mechanisms that define DNA replication origins in eukaryotes.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1186/gb-2012-13-4-r27
