A classical example of "transcriptional silencing" is found in the yeast S. cerevisiae mating-type switch [1, 2]. The gene pairs a1/a2 and α1/α2, positioned at the loci HMR and HML, respectively, are silenced by Sir proteins recruited by proteins that bind sites flanking each locus. Transfer of either gene pair to the Sir-free MAT locus, or mutation of the Sirs, allows expression of those genes at levels sufficient to foster yeast mating. Here we confirm that, in the absence of Sirs, a1 and a2 at HMR are expressed at low levels . This level is low because, we show, the relevant transcriptional activators, which work from regulatory sites located between the divergently transcribed genes, are weak. That property-weak activation-is a prerequisite for effective silencing upon recruitment of Sirs. We use our quantitative nucleosome occupancy assay to show that Sirs (which bind nucleosomes) increase the avidities with which those nucleosomes form at the promoters. That increase can account for at least part of the repressive effects of the Sirs and can explain why silencing is effective in countering weak activation only. We suggest that "silencing" in higher eukaryotes (e.g., by Polycomb or HP1) follows similar rules [4, 5] and note where such effects could be important.
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