Transcription mediated insulation and interference direct gene cluster expression switches.
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.
['Nguyen|Tania|T|', 'Fischl|Harry|H|', 'Howe|Françoise S|FS|', 'Woloszczuk|Ronja|R|', 'Serra Barros|Ana|A|', 'Xu|Zhenyu|Z|', 'Brown|David|D|', 'Murray|Struan C|SC|', 'Haenni|Simon|S|', 'Halstead|James M|JM|', "O'Connor|Leigh|L|", 'Shipkovenska|Gergana|G|', 'Steinmetz|Lars M|LM|', 'Mellor|Jane|J|']
D002244:Carbon D015966:Gene Expression Regulation, Fungal D005800:Genes, Fungal D056426:Genetic Loci D053858:Metabolic Networks and Pathways D005810:Multigene Family D016372:RNA, Antisense D012333:RNA, Messenger D012441:Saccharomyces cerevisiae D029701:Saccharomyces cerevisiae Proteins D014157:Transcription Factors D014158:Transcription, Genetic
gene clusters genes transcription interference transcription insulation HMS2:BAT2 S. cerevisiae chromosomes computational biology cycling transcripts systems biology yeast metabolic cycle