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

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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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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-000E-A115-1 Version Permalink: https://hdl.handle.net/11858/00-001M-0000-000E-A116-0

Genre: Journal Article

Alternative Title : J. Biol. Chem.

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Zschocke, J¹, Author
Manthey, D¹, Author
Bayatti, N¹, Author
van der Burg, B¹, Author
Goodenough, S¹, Author
Behl, C¹, Author

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1Max Planck Institute of Psychiatry, Max Planck Society, ou_1607137

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Abstract: 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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Language(s): eng - English

Dates: Date issued: 2002-10-11

Publication Status: Issued

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Rev. Type: Peer

Identifiers: eDoc: 4059
ISI: 000178529600097

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Title: Journal of Biological Chemistry

Alternative Title : J. Biol. Chem.

Source Genre: Journal

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Pages: - Volume / Issue: 277 (41) Sequence Number: - Start / End Page: 38772 - 38780 Identifier: ISSN: 0021-9258