SPECIFIC REPRESSION OF THE YEAST SILENT MATING LOCUS HMR BY AN ADJACENT TELOMERE

The yeast silent mating loci HML and HMR are located at opposite ends of chromosome III adjacent to the telomeres. Mutations in the N termin us of histone H4 have been previously found to derepress the yeast sil ent mating locus HML to a much greater extent than HMR. Although diffe rences in the a and alpha mating-type regulatory genes and in the cis- acting silencer elements do not appear to strongly influence the level of derepression at HMR, we have found that the differential between t he two silent cassettes is largely due to the position of the HMR cass ette relative to the telomere on chromosome III. While HML is derepres sed to roughly the same extent by mutations in histone H4 regardless o f its chromosomal location, HMR is affected to different extents depen ding upon its chromosomal positioning. We have found that HMR is more severely derepressed by histone H4 mutations when positioned far from the telomere (cdc14 locus on chromosome VI) but is only minimally affe cted by the same mutations when integrated immediately adjacent to ano ther telomere (ADH4 locus on chromosome VII). These data indicate that the degree of silencing at HMR is regulated in part by its neighborin g telomere over a distance of at least 23 kb and that this form of reg ulation is unique for HMR and not present at HML. These data also indi cate that histone H4 plays an important role in regulating the silence d state at both HML and HMR.