Nucleic Acids Research Advance Access originally published online on November 13, 2007
Nucleic Acids Research 2008 36(1):144-156; doi:10.1093/nar/gkm986
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Nucleic Acids Research, 2008, Vol. 36, No. 1 144-156
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Genomics |
Genomic distribution and functional analyses of potential G-quadruplex-forming sequences in Saccharomyces cerevisiae
1College of Arts and Sciences and Vagelos Scholars Program, University of Pennsylvania, 2Department of Pathology and Laboratory Medicine, 3Cell and Molecular Biology Graduate Program, 4Penn Center for Bioinformatics, and 5Penn Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
*To whom correspondence should be addressed. Tel: 215-573-5037; Fax: 215-573-6317; Email: johnsonb{at}mail.med.upenn.edu
Received September 9, 2007. Revised October 14, 2007. Accepted October 19, 2007.
Although well studied in vitro, the in vivo functions of G-quadruplexes (G4-DNA and G4-RNA) are only beginning to be defined. Recent studies have demonstrated enrichment for sequences with intramolecular G-quadruplex forming potential (QFP) in transcriptional promoters of humans, chickens and bacteria. Here we survey the yeast genome for QFP sequences and similarly find strong enrichment for these sequences in upstream promoter regions, as well as weaker but significant enrichment in open reading frames (ORFs). Further, four findings are consistent with roles for QFP sequences in transcriptional regulation. First, QFP is correlated with upstream promoter regions with low histone occupancy. Second, treatment of cells with N-methyl mesoporphyrin IX (NMM), which binds G-quadruplexes selectively in vitro, causes significant upregulation of loci with QFP-possessing promoters or ORFs. NMM also causes downregulation of loci connected with the function of the ribosomal DNA (rDNA), which itself has high QFP. Third, ORFs with QFP are selectively downregulated in sgs1 mutants that lack the G4-DNA-unwinding helicase Sgs1p. Fourth, a screen for yeast mutants that enhance or suppress growth inhibition by NMM revealed enrichment for chromatin and transcriptional regulators, as well as telomere maintenance factors. These findings raise the possibility that QFP sequences form bona fide G-quadruplexes in vivo and thus regulate transcription.
Present address: Julia Y. Lee, Department of Biology, Saint Joseph's University, Philadelphia, PA.
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