Histone acetylation is associated with transcriptional activation of many genes. However, the role of acetylation in transcriptional regulation of heat shock protein genes (hsp) still remains an obscure issue. Here we examined the effects of historic deacetylase inhibitors (HDIs), trichostatin A, and sodium butyrate, on changes in acetylation level of core histories and on expression of hsp22 gene in Drosophila melanogaster. The results showed that both HDIs elevated flit! acetylation level of historic H3. By using the chromatin immunoprecipitation, we located the HDI-induced H3 hyperacetylation at both the promoter and the downstream of RNA polymerase 11 of the transcribing hsp22 gene. Meanwhile, the elevated acetylation level increased the accessibility of heat shock factor to target cis-acting regulatory sites. We conclude that historic acetylation stimulates the transcription initiation and promotes the transcription elongation, thereby up-regulating both basal and inducible expression of hsp22 in D. melanogaster. (C) 2004 Elsevier Inc. All rights reserved.