Genome-wide depletion of replication initiation events in highly transcribed regions

Melvenia M. Martin, Michael Ryan, RyangGuk Kim, Anna L. Zakas, Haiqing Fu, Chii Mei Lin, William C. Reinhold, Sean R. Davis, Sven Bilke, Hongfang D Liu, James H. Doroshow, Mark A. Reimers, Manuel S. Valenzuela, Yves Pommier, Paul S. Meltzer, Mirit I. Aladjem

Research output: Contribution to journalArticle

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Abstract

This report investigates the mechanisms by which mammalian cells coordinate DNA replication with transcription and chromatin assembly. In yeast, DNA replication initiates within nucleosome-free regions, but studies in mammalian cells have not revealed a similar relationship. Here, we have used genome-wide massively parallel sequencing to map replication initiation events, thereby creating a database of all replication initiation sites within nonrepetitive DNA in two human cell lines. Mining this database revealed that genomic regions transcribed at moderate levels were generally associated with high replication initiation frequency. In genomic regions with high rates of transcription, very few replication initiation events were detected. High-resolution mapping of replication initiation sites showed that replication initiation events were absent from transcription start sites but were highly enriched in adjacent, downstream sequences. Methylation of CpG sequences strongly affected the location of replication initiation events, whereas histone modifications had minimal effects. These observations suggest that high levels of transcription interfere with formation of pre-replication protein complexes. Data presented here identify replication initiation sites throughout the genome, providing a foundation for further analyses of DNA-replication dynamics and cell-cycle progression.

Original languageEnglish (US)
Pages (from-to)1822-1832
Number of pages11
JournalGenome Research
Volume21
Issue number11
DOIs
StatePublished - Nov 2011

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DNA Replication
Genome
Histone Code
Databases
High-Throughput Nucleotide Sequencing
Chromatin Assembly and Disassembly
Nucleosomes
Transcription Initiation Site
Methylation
Cell Cycle
Yeasts
Cell Line
DNA
Proteins

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Martin, M. M., Ryan, M., Kim, R., Zakas, A. L., Fu, H., Lin, C. M., ... Aladjem, M. I. (2011). Genome-wide depletion of replication initiation events in highly transcribed regions. Genome Research, 21(11), 1822-1832. https://doi.org/10.1101/gr.124644.111

Genome-wide depletion of replication initiation events in highly transcribed regions. / Martin, Melvenia M.; Ryan, Michael; Kim, RyangGuk; Zakas, Anna L.; Fu, Haiqing; Lin, Chii Mei; Reinhold, William C.; Davis, Sean R.; Bilke, Sven; Liu, Hongfang D; Doroshow, James H.; Reimers, Mark A.; Valenzuela, Manuel S.; Pommier, Yves; Meltzer, Paul S.; Aladjem, Mirit I.

In: Genome Research, Vol. 21, No. 11, 11.2011, p. 1822-1832.

Research output: Contribution to journalArticle

Martin, MM, Ryan, M, Kim, R, Zakas, AL, Fu, H, Lin, CM, Reinhold, WC, Davis, SR, Bilke, S, Liu, HD, Doroshow, JH, Reimers, MA, Valenzuela, MS, Pommier, Y, Meltzer, PS & Aladjem, MI 2011, 'Genome-wide depletion of replication initiation events in highly transcribed regions', Genome Research, vol. 21, no. 11, pp. 1822-1832. https://doi.org/10.1101/gr.124644.111
Martin, Melvenia M. ; Ryan, Michael ; Kim, RyangGuk ; Zakas, Anna L. ; Fu, Haiqing ; Lin, Chii Mei ; Reinhold, William C. ; Davis, Sean R. ; Bilke, Sven ; Liu, Hongfang D ; Doroshow, James H. ; Reimers, Mark A. ; Valenzuela, Manuel S. ; Pommier, Yves ; Meltzer, Paul S. ; Aladjem, Mirit I. / Genome-wide depletion of replication initiation events in highly transcribed regions. In: Genome Research. 2011 ; Vol. 21, No. 11. pp. 1822-1832.
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