title: Functional interaction of estrogen receptor alpha and caveolin isoforms in neuronal SK-N-MC cells.
abstract: Estrogen receptors (ERs) are expressed in neuronal cells and exhibit a wide variety of activities in the central nervous system. The actions of ERs are regulated in a hormone-dependent manner as well as by a number of co-activators and -repressors. A recently identified co-activator of ERalpha is caveolin-1 which has been shown to mediate the ligand-independent activation of this steroid receptor. In the present study we have demonstrated that neuronal SK-N-MC cells lacking functional ERalpha show high levels of caveolin-1/-2 specific transcripts and proteins. Ectopic expression of ERalpha in SK-N-MC cells leads to the transcriptional suppression of caveolin-1 and -2 genes. This silencing event is accompanied by changes in the methylation pattern of the caveolin-1 promoter. Certain CpG dinucleotides were methylated in the caveolin-1 promoter region of the SK-ERalpha cells whereas the same sites were non-methylated in control SK-N-MC cells, implicating a gene silencing mechanism including hypermethylation of DNA. In addition, inhibitors of methyltransferases or histone deacetylases, enzymes involved in the establishment and maintenance of silenced chromatin status, partially restored caveolin transcription in SK-ERalpha cells. In conclusion, our observations provide a possible mechanism of negative feedback regulation of ERalpha co-activator caveolin by the steroid receptor itself in this cellular model.
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, Johannes Gutenberg University, 55099 Mainz, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Zschocke
authors.forename: Dieter
authors.initials: D
authors.lastname: Manthey
authors.forename: Nadhim
authors.initials: N
authors.lastname: Bayatti
authors.forename: Christian
authors.initials: C
authors.lastname: Behl
mesh_terms: D001921:Brain / Q000378:metabolism; D051242:Caveolin 1; D022461:Caveolins / Q000737:chemistry* / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D018899:CpG Islands; D015254:DNA Modification Methylases / Q000378:metabolism; D047628:Estrogen Receptor alpha; D006655:Histone Deacetylases / Q000378:metabolism; D006728:Hormones / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008745:Methylation; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020033:Protein Isoforms; D011960:Receptors, Estrogen / Q000737:chemistry* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D002843:Chromatin; D047628:Estrogen Receptor alpha; D006728:Hormones; D008024:Ligands; D020033:Protein Isoforms; D011960:Receptors, Estrogen; D015254:DNA Modification Methylases; D006655:Histone Deacetylases