Transcriptional cosuppression of yeast Ty1 retrotransposons

Abstract

Cosuppression, the silencing of dispersed homologous genes triggered by high copy number, may have evolved in eukaryotic organisms to control molecular parasites such as viruses and transposons.Ty1 retrotransposons are dispersed gene repeats inSaccharomyces cerevisiae, where no cosuppression has been previously observed. Ty1 elements are seemingly expressed undeterred to a level as high as 10% of total mRNA. UsingTy1–URA3 reporters and negative selection with 5-fluoroorotic acid, it is shown that Ty1 genes can undergo transcriptional cosuppression that is independent of DNA methylation and polycomb-mediated repression. Expression of Ty1-related genes was shown to be in one of two states, the coexpressed state with allTy1-related genes transcribed or the cosuppressed state with all Ty1-related genes shut off, without uncoordinated or mosaic expression in any individual cell. Rapid switches between the two states were observed. A high copy number of Ty1 elements was shown to be required for the initiation of Ty1homology-dependent gene silencing, implying that Ty1 gene expression is under negative feedback control. Ty1transcriptional repressors facilitated the onset of Ty1cosuppression, and the native Ty1 promoters were required forTy1 cosuppression, indicating that Ty1 cosuppression occurs at the transcriptional level.

Keywords

• Cosuppression
• Ty1
• transcription
• retrotransposition
• DNA methylation