English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

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

MPS-Authors

Zschocke,  J
Max Planck Institute of Psychiatry, Max Planck Society;

Manthey,  D
Max Planck Institute of Psychiatry, Max Planck Society;

Bayatti,  N
Max Planck Institute of Psychiatry, Max Planck Society;

van der Burg,  B
Max Planck Institute of Psychiatry, Max Planck Society;

Goodenough,  S
Max Planck Institute of Psychiatry, Max Planck Society;

Behl,  C
Max Planck Institute of Psychiatry, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

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.


Cite as: https://hdl.handle.net/11858/00-001M-0000-000E-A115-1
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