| Autor: |
Nguyen T; Department of Biochemistry, University of Oxford, Oxford, United Kingdom., Fischl H; Department of Biochemistry, University of Oxford, Oxford, United Kingdom., Howe FS; Department of Biochemistry, University of Oxford, Oxford, United Kingdom., Woloszczuk R; Department of Biochemistry, University of Oxford, Oxford, United Kingdom., Serra Barros A; Department of Biochemistry, University of Oxford, Oxford, United Kingdom., Xu Z; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Brown D; Department of Biochemistry, University of Oxford, Oxford, United Kingdom., Murray SC; Department of Biochemistry, University of Oxford, Oxford, United Kingdom., Haenni S; Department of Biochemistry, University of Oxford, Oxford, United Kingdom., Halstead JM; Department of Biochemistry, University of Oxford, Oxford, United Kingdom., O'Connor L; Department of Biochemistry, University of Oxford, Oxford, United Kingdom., Shipkovenska G; Department of Biochemistry, University of Oxford, Oxford, United Kingdom., Steinmetz LM; Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany., Mellor J; Department of Biochemistry, University of Oxford, Oxford, United Kingdom. |
| Abstrakt: |
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. |
