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Gelsolin gene silencing involving unusual hypersensitivities to dimethylsulfate and KMnO4 in vivo footprinting on its promoter region

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Title: Gelsolin gene silencing involving unusual hypersensitivities to dimethylsulfate and KMnO4 in vivo footprinting on its promoter region
Other Titles: Gene silencing of gelsolin in bladder cancer
Authors: Haga, Kazunori Browse this author
Fujita, Hisakazu Browse this author
Nomoto, Minoru Browse this author
Sazawa, Ataru Browse this author
Nakagawa, Koji Browse this author
Harabayashi, Toru Browse this author
Shinohara, Nobuo Browse this author
Takimoto, Masato Browse this author
Nonomura, Katsuya Browse this author
Kuzumaki, Noboru10 Browse this author
Authors(alt): 葛巻, 暹10
Keywords: gelsolin
gene silencing
dimethylsulfate hypersensitivity
bladder cancer
in vivo footprinting
Issue Date: 20-May-2004
Publisher: Wiley-Liss, Inc.
Journal Title: International Journal of Cancer
Volume: 111
Issue: 6
Start Page: 873
End Page: 880
Publisher DOI: 10.1002/ijc.20348
PMID: 15300799
Abstract: We previously reported that gelsolin gene expression is reduced in various tumors. In an effort to gain further insights into the mechanism of gelsolin downregulation in tumors, we examined the in vivo properties of the gelsolin promoter in urinary bladder cancer cell lines. Neither mutation nor hypermethylation were responsible for gene silencing at the promoter. After exposure to trichostatin A (TSA), a histone deacetylase inhibitor, gelsolin promoter activity was markedly enhanced in the cancer cells not in cells derived from normal tissue. Chromatin immunoprecipitation (ChIP) assays revealed that both histones H3 and H4 were hypoacetylated in the promoter region of the cancer cells, and the accumulation of acetylated histones were detected by TSA treatment. In vivo footprinting analysis revealed the presence of dimethylsulfate (DMS) hypersensitive site in the untranslated region around nucleotide -35 only in the cancer cells but not in cells derived from normal tissue, and analysis of KMnO4 reactive nucleotides showed that the stem loop structure could be formed in vivo of the cancer cells. This novel stem loop structure may play a part in regulating the transcription of the gelsolin gene in the cancer cells. .. These results suggest that nucleosome accessibility through histone deacetylation and structural changes (DMS hypersensitivity and stem loop structure) in the promoter region form the basis of the mechanism leading to the silencing of gelsolin gene in human bladder cancer.
Rights: Copyright (c) 2004 Wiley-Liss, Inc
Type: article (author version)
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 葛巻 暹

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