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  Estrogen receptor alpha-mediated silencing of caveolin gene expression in neuronal cells

Zschocke, J., Manthey, D., Bayatti, N., van der Burg, B., Goodenough, S., & Behl, C. (2002). Estrogen receptor alpha-mediated silencing of caveolin gene expression in neuronal cells. Journal of Biological Chemistry, 277(41), 38772-38780.

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資料種別: 学術論文
その他のタイトル : J. Biol. Chem.

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 作成者:
Zschocke, J1, 著者
Manthey, D1, 著者
Bayatti, N1, 著者
van der Burg, B1, 著者
Goodenough, S1, 著者
Behl, C1, 著者
所属:
1Max Planck Institute of Psychiatry, Max Planck Society, ou_1607137              

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 要旨: Estrogen receptors (ERalpha/ERbeta) are expressed in neuronal cells and exhibit a variety of activities in the central nervous system. ER activity is regulated in a ligand-dependent manner and by co-regulatory factors. Caveolin-1 is a recently identified co-activator of ERalpha mediating the ligand- independent activation of this steroid receptor. Here the influence of ERs on caveolin expression in human neuroblastoma SK-N-MC cells as well as in rodent brain was investigated. We found that ectopic expression of ERalpha in SK-N-MC cells (SK- ERalpha) leads to a ligand-independent transcriptional suppression of caveolin-1/-2 genes. This suppression is specifically mediated by ERalpha and not ERbeta because ERbeta counteracts the observed caveolin-silencing process. Interestingly, decreased caveolin expression in SK-ERalpha is accompanied by changes in the methylation pattern of caveolin promoters. The analysis of selected promoter regions of the human caveolin-1 gene showed that certain CpG dinucleotides were hypermethylated in SK-ERalpha cells, whereas the same sites were unmethylated in control, ERbeta-, and ERalpha/beta co-expressing SK-N-MC cells. Inhibition of DNA methylation or histone deacetylation led to partial re-expression of caveolin- 1/-2 genes in SK-ERalpha. In vivo analysis revealed a down- regulation of caveolin-1 expression after long term estrogen exposure in certain regions of the mouse brain. In conclusion, we have shown for the first time that ERalpha and not ERbeta silences caveolin-1/-2 expression in an epigenetic fashion in neuronal cells. The observed mechanism of gene silencing by ERalpha may have implications for the transcriptional regulation of further ERalpha target gene

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言語: eng - English
 日付: 2002-10-11
 出版の状態: 出版
 ページ: -
 出版情報: -
 目次: -
 査読: 査読あり
 識別子(DOI, ISBNなど): eDoc: 4059
ISI: 000178529600097
 学位: -

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出版物 1

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出版物名: Journal of Biological Chemistry
  出版物の別名 : J. Biol. Chem.
種別: 学術雑誌
 著者・編者:
所属:
出版社, 出版地: -
ページ: - 巻号: 277 (41) 通巻号: - 開始・終了ページ: 38772 - 38780 識別子(ISBN, ISSN, DOIなど): ISSN: 0021-9258