| pubmed-article:15544930 | pubmed:abstractText | Estrogen receptor-alpha (ER alpha) regulates transcription through a number of molecular mechanisms. Two mechanisms by which ER alpha acts directly in the nucleus have emerged: (1) in classical ER alpha action, estrogen-bound receptor binds estrogen response elements (ERE) and regulates promoters by recruiting coactivators or corepressors to DNA; (2) non-classical action is not dependent on ER alpha binding to EREs; its mechanism is not as clearly defined as classical action. In many instances, non-classical action is mediated by tethering of ER alpha to other DNA-binding proteins, facilitating recruitment of coregulators to transcription regulatory sequences. In some cell types, non-classical stimulation can be enhanced by antagonists and repressed by agonists of ER alpha. Here, we show that non-classical action of ER alpha in 293 cells occurs in a wide range of enhancers and enhancer binding proteins. ER alpha stimulates AP-1 elements, cyclic AMP response elements (CRE), and serum response elements (SRE) in the presence of the antiestrogen ICI182,780. Further, in the presence of ICI182,780, ER alpha stimulates activation domains of Jun, ATF-2, Elk, and CRE-binding protein (CREB). Non-classical ER alpha regulation described here does not appear to be sensitive to point mutations which affect classical and tethered ER alpha action; moreover, in our experiments, non-classical action is uniquely sensitive to nuclear transport inhibition by leptomycin B. Because ICI182,780 appears to affect multiple and diverse transcriptional systems, our results are likely explained by ER alpha-dependent modulation of common components of the transcriptional machinery and may not be completely explained by tethering of ER alpha to specific transcription factors. | lld:pubmed |
