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

Oncogene volume 23, pages 1704–1711 (2004)Cite this article

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.

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Acknowledgements

We are grateful to Drs ER Fearon for plasmid constructs, and to SY Rha and HC Chung for their help of cDNA microarray analysis. We also thank Dr H Kleinman for critical reading and comments of the manuscript. This study was supported by a grant from the Korea Science & Engineering Foundation (R01-1999-00121-0) and the Brain Korea 21 Project.

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  1. Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, 98 Kunja-dong, Kwangjin-gu, Seoul, 143-747, Korea

    Joong Sup Shim, Dong Hoon Kim & Ho Jeong Kwon

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Correspondence to Ho Jeong Kwon.

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Shim, J., Kim, D. & Kwon, H. Plakoglobin is a new target gene of histone deacetylase in human fibrosarcoma HT1080 cells. Oncogene 23, 1704–1711 (2004). https://doi.org/10.1038/sj.onc.1207289

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