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Estrogen response element-dependent regulation of transcriptional activation of estrogen receptors α and β by coactivators and corepressors
| Content Provider | Semantic Scholar |
|---|---|
| Author | Klinge, Carolyn M. Jernigan, Sarah C. Mattingly, Kathleen A. Risinger, Kelly E. Zhang, Jianwei |
| Copyright Year | 2004 |
| Abstract | One mechanism by which ligand-activated estrogen receptors and (ER and ER) stimulate gene transcription is through direct ER interaction with specific DNA sequences, estrogen response elements (EREs). ERE-bound ER recruits coactivators that stimulate gene transcription. Binding of ER to natural and synthetic EREs with different nucleotide sequences alters ER binding affinity, conformation, and transcriptional activity, indicating that the ERE sequence is an allosteric effector of ER action. Here we tested the hypothesis that alterations in ER conformation induced by binding to different ERE sequences modulates ER interaction with coactivators and corepressors. CHO-K1 cells transfected with ER or ER show ERE sequence-dependent differences in the functional interaction of ER and ER with coactivators steroid receptor coativator 1 (SRC-1), SRC-2 (glucocorticoid receptor interacting protein 1 (GRIP1)), SRC-3 amplified in breast cancer 1 (AIB1) and ACTR, cyclic AMP binding protein (CBP), and steroid receptor RNA activator (SRA), corepressors nuclear receptor co-repressor (NCoR) and silencing mediator for retinoid and thyroid hormone recpetors (SMRT), and secondary coactivators coactivator associated arginine methyltransferase 1 (CARM1) and protein arginine methyltransferase 1 (PRMT1). We note both ligand-independent as well estradiol- and 4-hydroxytamoxifen-dependent differences in ER-coregulator activity. In vitro ER-ERE binding assays using receptor interaction domains of these coregulators failed to recapitulate the cell-based results, substantiating the importance of the full-length proteins in regulating ER activity. These data demonstrated that the ERE sequence impacts estradioland 4-hydroxytamoxifen-occupied ER and ER interaction with coregulators as measured by transcriptional activity in mammalian cells. |
| Starting Page | 387 |
| Ending Page | 410 |
| Page Count | 24 |
| File Format | PDF HTM / HTML |
| DOI | 10.1677/jme.1.01541 |
| Volume Number | 33 |
| Alternate Webpage(s) | https://jme.bioscientifica.com/downloadpdf/journals/jme/33/2/0330387.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
