title: The Role of Transcription Factors at Antisense-Expressing Gene Pairs in Yeast.
abstract: Genes encoded close to one another on the chromosome are often coexpressed, by a mechanism and regulatory logic that remain poorly understood. We surveyed the yeast genome for tandem gene pairs oriented tail-to-head at which expression antisense to the upstream gene was conserved across species. The intergenic region at most such tandem pairs is a bidirectional promoter, shared by the downstream gene mRNA and the upstream antisense transcript. Genomic analyses of these intergenic loci revealed distinctive patterns of transcription factor regulation. Mutation of a given transcription factor verified its role as a regulator in trans of tandem gene pair loci, including the proximally initiating upstream antisense transcript and downstream mRNA and the distally initiating upstream mRNA. To investigate cis-regulatory activity at such a locus, we focused on the stress-induced NAD(P)H dehydratase YKL151C and its downstream neighbor, the metabolic enzyme GPM1 Previous work has implicated the region between these genes in regulation of GPM1 expression; our mutation experiments established its function in rich medium as a repressor in cis of the distally initiating YKL151C sense RNA, and an activator of the proximally initiating YKL151C antisense RNA. Wild-type expression of all three transcripts required the transcription factor Gcr2. Thus, at this locus, the intergenic region serves as a focal point of regulatory input, driving antisense expression and mediating the coordinated regulation of YKL151C and GPM1 Together, our findings implicate transcription factors in the joint control of neighboring genes specialized to opposing conditions and the antisense transcripts expressed between them.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California Present address: Cardiovascular Research Institute, University of California, San Francisco, CA.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Mostovoy
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California Program in Molecular Medicine, Friedrich-Schiller-Universität, Jena, Germany Present address: Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN.
authors.forename: Alexander
authors.initials: A
authors.lastname: Thiemicke
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California Present address: Graduate Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA.
authors.forename: Tiffany Y
authors.initials: TY
authors.lastname: Hsu
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California Present address: Buck Institute for Research on Aging, Novato, CA rbrem@buckinstitute.org.
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Brem
mesh_terms: D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D011401:Promoter Regions, Genetic; D016372:RNA, Antisense / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D025842:SUMO-1 Protein / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: C076228:GCR2 protein, S cerevisiae; C000614612:Gmp1 protein, S cerevisiae; D016372:RNA, Antisense; D012333:RNA, Messenger; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors
keywords: antisense transcription; gene regulation; non-coding RNA