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.

Transcriptionally silent chromatin is associated with reduced histone acetylation and its propagation depends on histone hypoacetylation promoted by histone deacetylases. We show that tethered histone acetyltransferase (HAT) Esa1p or Gcn5p creates a segment of hyperacetylated chromatin that is at least 2.6 kb in size and counteracts transcriptional silencing that emanates from a silencer in yeast. Esa1p and Gcn5p counteract URA3 silencing even when they are targeted 1.7 kb downstream of the promoter and >2.0 kb from the silencer. The anti-silencing effect of a targeted HAT is strengthened by increasing the number of targeting sites, but impaired by events that enhance silencing. A tethered HAT can also counteract telomeric silencing. The anti-silencing effect of Gcn5p is abolished by a mutation that eliminated its HAT activity or by deleting the ADA2 gene encoding a structural component of Gcn5p-containing HAT complexes. These results demonstrate that a tethered HAT complex can create a sizable region of histone hyperacetylation and serve as a barrier to encroaching repressive chromatin.