Transcription mediated insulation and interference direct gene cluster expression switches

• Published in: eLife Vol. 3; p. e03635
• Main Authors: Nguyen, Tania, Fischl, Harry, Howe, Françoise S, Woloszczuk, Ronja, Serra Barros, Ana, Xu, Zhenyu, Brown, David, Murray, Struan C, Haenni, Simon, Halstead, James M, O'Connor, Leigh, Shipkovenska, Gergana, Steinmetz, Lars M, Mellor, Jane
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 19.11.2014; eLife Sciences Publications, Ltd
• Subjects: Antisense RNA; Carbon; Carbon - pharmacology; Carbon sources; Cell division; Computational and Systems Biology; cycling transcript; gene cluster; Gene clusters; Gene expression; Gene Expression Regulation, Fungal; Gene regulation; Genes and Chromosomes; Genes, Fungal; Genetic Loci; Genomes; Glucose; HMS2:BAT2; Metabolic Networks and Pathways - drug effects; Metabolism; Molecular biology; Multigene Family; RNA polymerase; RNA, Antisense - genetics; RNA, Antisense - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Transcription factors; Transcription Factors - metabolism; transcription insulation; transcription interference; Transcription, Genetic; yeast metabolic cycle; computational biology; systems biology; HMS2:BAT2; cycling transcripts; transcription insulation; gene clusters; genes; chromosomes; transcription interference; yeast metabolic cycle; S. cerevisiae
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.03635

In yeast, many tandemly arranged genes show peak expression in different phases of the metabolic cycle (YMC) or in different carbon sources, indicative of regulation by a bi-modal switch, but it is not clear how these switches are controlled. Using native elongating transcript analysis (NET-seq), we show that transcription itself is a component of bi-modal switches, facilitating reciprocal expression in gene clusters. HMS2, encoding a growth-regulated transcription factor, switches between sense- or antisense-dominant states that also coordinate up- and down-regulation of transcription at neighbouring genes. Engineering HMS2 reveals alternative mono-, di- or tri-cistronic and antisense transcription units (TUs), using different promoter and terminator combinations, that underlie state-switching. Promoters or terminators are excluded from functional TUs by read-through transcriptional interference, while antisense TUs insulate downstream genes from interference. We propose that the balance of transcriptional insulation and interference at gene clusters facilitates gene expression switches during intracellular and extracellular environmental change.