title: Local potentiation of stress-responsive genes by upstream noncoding transcription.
abstract: It has been postulated that a myriad of long noncoding RNAs (lncRNAs) contribute to gene regulation. In fission yeast, glucose starvation triggers lncRNA transcription across promoter regions of stress-responsive genes including fbp1 (fructose-1,6-bisphosphatase1). At the fbp1 promoter, this transcription promotes chromatin remodeling and fbp1 mRNA expression. Here, we demonstrate that such upstream noncoding transcription facilitates promoter association of the stress-responsive transcriptional activator Atf1 at the sites of transcription, leading to activation of the downstream stress genes. Genome-wide analyses revealed that ∼50 Atf1-binding sites show marked decrease in Atf1 occupancy when cells are treated with a transcription inhibitor. Most of these transcription-enhanced Atf1-binding sites are associated with stress-dependent induction of the adjacent mRNAs or lncRNAs, as observed in fbp1 These Atf1-binding sites exhibit low Atf1 occupancy and high histone density in glucose-rich conditions, and undergo dramatic changes in chromatin status after glucose depletion: enhanced Atf1 binding, histone eviction, and histone H3 acetylation. We also found that upstream transcripts bind to the Groucho-Tup1 type transcriptional corepressors Tup11 and Tup12, and locally antagonize their repressive functions on Atf1 binding. These results reveal a new mechanism in which upstream noncoding transcription locally magnifies the specific activation of stress-inducible genes via counteraction of corepressors.
authors.affiliation: Department of Life Sciences, The University of Tokyo, Meguro-ku, Tokyo 153-8902, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Takemata
authors.affiliation: Department of Life Sciences, The University of Tokyo, Meguro-ku, Tokyo 153-8902, Japan.
authors.forename: Arisa
authors.initials: A
authors.lastname: Oda
authors.affiliation: Department of Biological Sciences, Chuo University, Bunkyo-ku, Tokyo 112-8551, Japan.
authors.forename: Takatomi
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0035, Japan.
authors.forename: Josephine
authors.initials: J
authors.lastname: Galipon
authors.affiliation: Department of Life Sciences, The University of Tokyo, Meguro-ku, Tokyo 153-8902, Japan.
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Miyoshi
authors.affiliation: Department of Medical Genome Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Medical Genome Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Sugano
authors.affiliation: Biology Department, Boston College, Chestnut Hill, MA 02467, USA.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Hoffman
authors.affiliation: Department of Chemistry, Tokyo Metropolitan University, Hachi-Ohji, Tokyo 192-0397, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Hirota
authors.affiliation: Department of Life Sciences, The University of Tokyo, Meguro-ku, Tokyo 153-8902, Japan Department of Biological Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan kohta@bio.c.u-tokyo.ac.jp.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Ohta
mesh_terms: D000107:Acetylation; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000378:metabolism; D011485:Protein Binding; D022661:RNA, Untranslated / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D022661:RNA, Untranslated; D029701:Saccharomyces cerevisiae Proteins; D005947:Glucose