Plakoglobin is a new target gene of histone deacetylase in human fibrosarcoma HT1080 cells

Joong Sup Shim, Dong Hoon Kim, Ho Jeong Kwon

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19 Citations (Scopus)

Abstract

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 β-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 (-945 ∼ -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.

Original languageEnglish
Pages (from-to)1704-1711
Number of pages8
JournalOncogene
Volume23
Issue number9
DOIs
Publication statusPublished - 2004 Mar 4

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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