title: Dual role of NRSF/REST in activation and repression of the glucocorticoid response.
abstract: 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.
authors.affiliation: Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel.
authors.forename: Lilach
authors.initials: L
authors.lastname: Abramovitz
authors.affiliation: Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Shapira
authors.affiliation: Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Ben-Dror
authors.affiliation: Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel.
authors.forename: Vardit
authors.initials: V
authors.lastname: Dror
authors.affiliation: Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel.
authors.forename: Limor
authors.initials: L
authors.lastname: Granot
authors.affiliation: Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Rousso
authors.affiliation: Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel.
authors.forename: Elad
authors.initials: E
authors.lastname: Landoy
authors.affiliation: Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Blau
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, University of Saarland Medical Center, D-66421 Homburg, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Thiel
authors.affiliation: Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel. Electronic address: vardi@post.tau.ac.il.
authors.forename: Lily
authors.initials: L
authors.lastname: Vardimon
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D019556:COS Cells; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002645:Chickens; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation / Q000187:drug effects*; D005822:Genetic Vectors / Q000235:genetics; D005938:Glucocorticoids / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D015003:Yeasts / Q000235:genetics / Q000378:metabolism; D000099229:RE1-Silencing Transcription Factor
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D012097:Repressor Proteins; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor