It is widely accepted that transcriptional regulation of eukaryotic genes is 
intimately coupled to covalent modifications of the underlying chromatin 
template, and in certain cases the functional consequences of these 
modifications have been characterized. Here we present evidence that gene 
activation in the silent heterochromatin of the yeast Saccharomyces cerevisiae 
can occur in the context of little, if any, covalent histone modification. Using 
a SIR-regulated heat shock-inducible transgene, hsp82-2001, and a natural 
drug-inducible subtelomeric gene, YFR057w, as models we demonstrate that 
substantial transcriptional induction (>200-fold) can occur in the context of 
restricted histone loss and negligible levels of H3K4 trimethylation, H3K36 
trimethylation and H3K79 dimethylation, modifications commonly linked to 
transcription initiation and elongation. Heterochromatic gene activation can 
also occur with minimal H3 and H4 lysine acetylation and without replacement of 
H2A with the transcription-linked variant H2A.Z. Importantly, absence of histone 
modification does not stem from reduced transcriptional output, since 
hsp82-ΔTATA, a euchromatic promoter mutant lacking a TATA box and with threefold 
lower induced transcription than heterochromatic hsp82-2001, is strongly 
hyperacetylated in response to heat shock. Consistent with negligible H3K79 
dimethylation, dot1Δ cells lacking H3K79 methylase activity show unimpeded 
occupancy of RNA polymerase II within activated heterochromatic promoter and 
coding regions. Our results indicate that large increases in transcription can 
be observed in the virtual absence of histone modifications often thought 
necessary for gene activation.