Dual Role of NRSF/REST in Activation and Repression of the Glucocorticoid Response
| Autor: | Tal Rousso, Tamar Shapira, Limor Granot, Gerald Thiel, Lior Blau, Vardit Dror, Elad Landoy, Iris Ben-Dror, Lily Vardimon, Lilach Abramovitz |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Transcriptional Activation
medicine.medical_specialty Transcription Genetic Blotting Western Genetic Vectors Biology Biochemistry Retina Receptors Glucocorticoid Glucocorticoid receptor Transcription (biology) Cell Line Tumor Yeasts Internal medicine Glutamine synthetase Chlorocebus aethiops medicine Animals Humans Immunoprecipitation Gene silencing Promoter Regions Genetic Receptor Glucocorticoids Molecular Biology Psychological repression Cells Cultured Binding Sites COS cells Alternative splicing Cell Biology Cell biology Repressor Proteins Endocrinology Gene Expression Regulation COS Cells Chickens HeLa Cells Transcription Factors |
| Zdroj: | Journal of Biological Chemistry. 283:110-119 |
| ISSN: | 0021-9258 |
| Popis: | Restriction of glutamine synthetase to the nervous system is mainly achieved through the mutual function of the glucocorticoid receptor and the neural restrictive silencing factor, NRSF/REST. Glucocorticoids induce glutamine synthetase expression in neural tissues while NRSF/REST represses the hormonal response in non-neural cells. NRSF/REST is a modular protein that contains two independent repression domains, at the N and C termini of the molecule, and is dominantly expressed in nonneural cells. Neural tissues express however splice variants, REST4/5, which contain the repression domain at the N, but not at the C terminus of the molecule. Here we show that full-length NRSF/REST or its C-terminal domain can inhibit almost completely the induction of gene transcription by glucocorticoids. By contrast, the N-terminal domain not only fails to repress the hormonal response but rather stimulates it markedly. The inductive activity of the N-terminal domain is mediated by hBrm, which is recruited to the promoter only in the concomitant presence of GR. Importantly, a similar inductive activity is also exerted by the splice variant REST4. These findings raise the possibility that NRSF/REST exhibits a dual role in regulation of glutamine synthetase. It represses gene induction in nonneural cells and enhances the hormonal response, via its splice variant, in the nervous system. |
| Databáze: | OpenAIRE |
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