Alterations in histone acetylation seem to play a central role in the repression of several important genes, such as tumor suppressor genes. Previously we reported that gelsolin expression was reduced in human urinary bladder cancers and that ectopically expressed gelsolin acted as a tumor suppressor1. We have examined the effects of trichostatin A (TSA), a specific histone deacetylase inhibitor, to examine the histone acetylation status of the gelsolin promoter region in bladder cancers. We measured gelsolin protein expression by western blotting in bladder cancer cell lines treated with various doses of TSA. We assessed promoter activities of the gelsolin gene by luciferase assays in both nontreated and TSA-treated bladder cancer cell lines. The acetylation status of histones linked to the gelsolin promoter was checked using chromatin immunoprecipitation and a dot blot assay. Gelsolin protein production was much reduced in cancer cell lines. Both re-expression and the promoter activity of gelsolin induced by TSA were dose- and time-dependent. An antibody that reacts with acetylated histones H3 and H4 immunoprecipitated chromatin containing the gelsolin promoter in the TSA-treated bladder cancer cells, but not in nontreated cells. These results suggest that TSA activated the gelsolin gene promoter through histone acetylation. In bladder cancer, the repression of the gelsolin gene is related to the deacetylation of histones to its promoter region. Together with the reported epigenetic changes in histone acetylation in breast cancers, acetylation-mediated gene silencing could be a common mechanism of gelsolin downregulation in several cancers.