Within eukaryotic genomes, repetitious sequences are often silenced. Within the Drosophila melanogaster fourth chromosome, the DNA transposon remnant 1360 is an effective target, promoting silencing of an adjacent hsp70-driven white gene; this results in a Position Effect Variegation (PEV) phenotype. However, outside of the fourth chromosome, PEV is only observed when the reporter construct P{1360, hsp70-white} is present within or close to a heterochromatic domain (Haynes et al 2006 Curr Biol 16: 2222-7). At the 1198 “landing pad” site at the base of chromosome arm 2L, a copy of either 1360 or Invader4 (a retrotransposon remnant) can switch a euchromatic region to a heterochromatic one, with increased HP1a and H3K9me2; here the variegating hsp70-white shows a ~2-fold decrease in expression (Sentmanat & Elgin, PNAS 109:14104-9). Recently we observed that 256 copies of a 36 bp lacO fragment induces even stronger PEV, an ~8-fold decrease in expression of the hsp70-white reporter at this site. Surprisingly, lacO mediated silencing shows an inverse temperature effect, with a loss of silencing at lower temperatures (G. Reuter; EG). A fragment with 310 copies of the GAA triplet repeat in the 1198 site similarly results in eight-fold silencing. All three cases exhibit a loss of silencing on introduction of HP1a mutations, confirming that heterochromatin assembly is required. While mutations in the H3K9 methyl transferase Su(var)3-9 are dominant suppressors of 1360- and GAA310-induced silencing, this is not the case for lacO-induced silencing at 25°C. We find that lacO-induced silencing, the PEV observed in the wm4 line, and the PEV phenotype of a reporter in the pericentric heterochromatin (118E-10 line), are all sensitive to nicotinamide, an HDAC inhibitor, supporting a general role for histone deacetylation in heterochromatin formation in Drosophila. The heterochromatin-based mechanism for silencing the tandem lacO repeats apparently differs in some important aspects from that used to silence TEs, while the silencing induced by GAA310 mimics that seen at TEs and in pericentric heterochromatin generally. Supported by NIH GM068388, NSF MCB-1243724, & NSF MCB-1517266.