title: Genomic distribution and functional analyses of potential G-quadruplex-forming sequences in Saccharomyces cerevisiae.
abstract: 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.
authors.affiliation: College of Arts and Sciences and Vagelos Scholars Program, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Steve G
authors.initials: SG
authors.lastname: Hershman
authors.forename: Qijun
authors.initials: Q
authors.lastname: Chen
authors.forename: Julia Y
authors.initials: JY
authors.lastname: Lee
authors.forename: Marina L
authors.initials: ML
authors.lastname: Kozak
authors.forename: Peng
authors.initials: P
authors.lastname: Yue
authors.forename: Li-San
authors.initials: LS
authors.lastname: Wang
authors.forename: F Brad
authors.initials: FB
authors.lastname: Johnson
mesh_terms: D004275:DNA, Ribosomal / Q000737:chemistry; D054856:G-Quadruplexes / Q000187:drug effects; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000502:physiology; D016681:Genome, Fungal; D023281:Genomics; D006657:Histones / Q000378:metabolism; D008652:Mesoporphyrins / Q000494:pharmacology; D009154:Mutation; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D016615:Telomere / Q000737:chemistry; D014158:Transcription, Genetic
chemical_list: D004275:DNA, Ribosomal; D006657:Histones; D008652:Mesoporphyrins; C065420:N-methylmesoporphyrin IX