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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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Genre: Zeitschriftenartikel
Alternativer Titel : J. Biol. Chem.

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 Urheber:
Zschocke, J1, Autor
Manthey, D1, Autor
Bayatti, N1, Autor
van der Burg, B1, Autor
Goodenough, S1, Autor
Behl, C1, Autor
Affiliations:
1Max Planck Institute of Psychiatry, Max Planck Society, ou_1607137              

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 Zusammenfassung: 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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Sprache(n): eng - English
 Datum: 2002-10-11
 Publikationsstatus: Erschienen
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 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: eDoc: 4059
ISI: 000178529600097
 Art des Abschluß: -

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Titel: Journal of Biological Chemistry
  Alternativer Titel : J. Biol. Chem.
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 277 (41) Artikelnummer: - Start- / Endseite: 38772 - 38780 Identifikator: ISSN: 0021-9258