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Vol. 16, No. 4, pp. 467-478, February 15, 2002
Department of Medical Biochemistry and Genetics, Texas A&M University
System Health Science Center, College Station, Texas 77843-1114, USA
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 in
Saccharomyces cerevisiae, where no cosuppression has been
previously observed. Ty1 elements are seemingly expressed
undeterred to a level as high as 10% of total mRNA. Using
Ty1-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 all
Ty1-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 Ty1
homology-dependent gene silencing, implying that Ty1 gene expression is under negative feedback control. Ty1
transcriptional repressors facilitated the onset of Ty1
cosuppression, and the native Ty1 promoters were required for
Ty1 cosuppression, indicating that Ty1 cosuppression
occurs at the transcriptional level.
[Key Words: Cosuppression; Ty1; transcription; retrotransposition; DNA methylation]
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