Cell-to-cell heterogeneity of phosphate gene expression in yeast is controlled by alternative transcription, 14-3-3 and Spl2

• Published in: Biochimica et biophysica acta. Gene regulatory mechanisms 2021-06, Vol.1864 (6-7), p.194714-194714, Article 194714
• Main Authors: Crooijmans, Marjolein E., Delzenne, Tijn O., Hensen, Tim, Darehei, Mina, de Winde, Johannes H., van Heusden, G. Paul H.
• Format: Article
• Language: English
• Subjects: Bimodal gene expression; Non-coding transcription; Phosphate metabolism; Saccharomyces cerevisiae; Transcription start site
• ISSN: 1874-9399; 1876-4320
• DOI: 10.1016/j.bbagrm.2021.194714

Dependent on phosphate availability the yeast Saccharomyces cerevisiae expresses either low or high affinity phosphate transporters. In the presence of phosphate yeast cells still express low levels of the high affinity phosphate transporter Pho84. The regulator Spl2 is expressed in approximately 90% of the cells, and is not expressed in the remaining cells. Here we report that deletion of RRP6, encoding an exonuclease degrading non-coding RNA, or BMH1, encoding the major 14-3-3 isoform, resulted in less cells expressing SPL2 and in increased levels of RNA transcribed from sequences upstream of the SPL2 coding region. SPL2 stimulates its own expression and that of PHO84 ensuing a positive feedback. Upon deletion of the region responsible for upstream SPL2 transcription almost all cells express SPL2. These results indicate that the cell-to-cell variation in PHO84 and SPL2 expression is dependent on a specific part of the SPL2 promoter and is controlled by Bmh1 and Spl2. •Expression of PHO84 and SPL2 is strongly induced in the absence of phosphate.•In the presence of phosphate SPL2 is expressed in a bimodal way.•Deletion of RRP6 or BMH1 resulted in a lower fraction of cells expressing SPL2.•These deletions increased levels of RNA translated from sequences upstream of SPL2.•Removal of upstream transcription resulted in SPL2 expression in all cells.