Histone deacetylase (HDAC) plays a key role in gene expression, by suppressing the transcription of a number of target genes. Identification of such genes is important for deciphering the functional role of HDAC. Here, using cancer gene-focused DNA microarray analysis, we identified plakoglobin as a new target gene of HDAC. Functional inhibition of HDAC by its specific inhibitors induced the expression of plakoglobin by eight-fold in human fibrosarcoma HT1080 cells. However, the expression of b-catenin, which is closely related to plakoglobin, was not altered, implying the specific function of HDAC in plakoglobin expression. Using antiacetyl-H4 antibody, chromatin immunoprecipitation analysis revealed that the distal region (
945B
646) of the promoter of plakoglobin is responsible for the HDAC-mediated repression of the gene. Moreover, the induced expression of plakoglobin by the inhibition of HDAC activated the Tcf/ Lef-dependent luciferase reporter gene, a well-known downstream effector of the Wnt signaling pathway. Furthermore, transient transfection of plakoglobin also activated Tcf/Lef reporter gene expression. Taken together, our results demonstrate that plakoglobin is a new target gene governed by HDAC, and that it acts as an oncogene in HT1080 cells.