title: Intergenic transcription causes repression by directing nucleosome assembly.
abstract: Transcription of non-protein-coding DNA (ncDNA) and its noncoding RNA (ncRNA) products are beginning to emerge as key regulators of gene expression. We previously identified a regulatory system in Saccharomyces cerevisiae whereby transcription of intergenic ncDNA (SRG1) represses transcription of an adjacent protein-coding gene (SER3) through transcription interference. We now provide evidence that SRG1 transcription causes repression of SER3 by directing a high level of nucleosomes over SRG1, which overlaps the SER3 promoter. Repression by SRG1 transcription is dependent on the Spt6 and Spt16 transcription elongation factors. Significantly, spt6 and spt16 mutations reduce nucleosome levels over the SER3 promoter without reducing intergenic SRG1 transcription, strongly suggesting that nucleosome levels, not transcription levels, cause SER3 repression. Finally, we show that spt6 and spt16 mutations allow transcription factor access to the SER3 promoter. Our results raise the possibility that transcription of ncDNA may contribute to nucleosome positioning on a genome-wide scale where, in some cases, it negatively impacts protein-DNA interactions.
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Hainer
authors.forename: Justin A
authors.initials: JA
authors.lastname: Pruneski
authors.forename: Rachel D
authors.initials: RD
authors.lastname: Mitchell
authors.forename: Robin M
authors.initials: RM
authors.lastname: Monteverde
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Martens
mesh_terms: D021901:DNA, Intergenic / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006609:High Mobility Group Proteins / Q000378:metabolism; D056488:Histone Chaperones; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism*; D050543:Phosphoglycerate Dehydrogenase / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013696:Temperature; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D021901:DNA, Intergenic; D004268:DNA-Binding Proteins; C541535:FACT protein, S cerevisiae; D006609:High Mobility Group Proteins; D056488:Histone Chaperones; D009687:Nuclear Proteins; D009707:Nucleosomes; C475586:SPN1 protein, S cerevisiae; C065456:SPT6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D035602:Transcriptional Elongation Factors; D050543:Phosphoglycerate Dehydrogenase; C493278:SER3 protein, S cerevisiae