Position effect on the directionality of silencer function in Saccharomyces cerevisiae

In Saccharomyces cerevisiae, silencers flanking the HML and HMR loci initiate the establishment of transcriptional silencing. We demonstrate that the activity of a silencer pertaining to its potency and directionality is dependent on its genomic position. The context of the HML-E silencer is more permissive to silencer function than that of HML-I or HMR-E, despite that HML-E and HML-I are only 3.3 kb apart. The apparent strength and directionality of a silencer in a particular location is affected by other silencing elements (silencers and protosilencers) present in its context. We show that at the HML locus, at least four silencing elements engage in multiple functional interactions that contribute to the activities of the silencers. Notably, these dispersed silencing elements can synergize to silence genes located not only inside, but also outside the HML sequence that harbors them. Moreover, the relative positions and orientations of these elements are important for silencing, indicating that they belong to an intricate silencing network.