Analysis of intergenic transcription as a regulator of gene expression in S. cerevisiae

Joseph A Martens, Lisa Laprade, Fred Winston. Genetics, Harvard Medical School, 77 Ave Louis Pasteur, Boston, MA, 02115, USA.

Recent studies in S. cerevisiae and in humans have demonstrated that transcription by RNA polymerase II is widespread, including genomic regions that do not encode proteins. The roles of such intergenic transcription are largely unknown. We have discovered a role for one case of intergenic transcription in studies of the S. cerevisiae SER3 gene. Our previous results demonstrated that transcription of SER3 is tightly repressed during growth in rich medium and that this repression requires the Swi/Snf chromatin remodeling complex. We now show that the SER3 regulatory region is highly transcribed under repressing conditions, producing a non-protein-coding RNA (SRG1). Expression of the SRG1 RNA is required for repression of SER3. Additional experiments have demonstrated that repression occurs by a transcription interference mechanism in which SRG1 transcription across the SER3 promoter interferes with the binding of activators. This work, then, identifies a previously unknown class of transcriptional regulatory gene. Additional questions currently being addressed include: 1) Is intergenic transcription a general mechanism of repression? 2) What is the relationship between Swi/Snf and SRG1 in repressing SER3 transcription? 3) How are these repression mechanisms overcome under conditions that induce SER3 transcription such as amino acid starvation? Our goal is to understand the physiological importance of intergenic transcription as a regulator of gene expression.

Program Nr. 369C from 2004 Yeast meeting

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