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Biological activity of RE‐1 silencing transcription factor (REST) towards distinct transcriptional activators
Author(s) -
Lietz Michael,
Bach Karl,
Thiel Gerald
Publication year - 2001
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.0953-816x.2001.01762.x
Subject(s) - repressor , psychological repression , transcription factor , transcription (linguistics) , gene silencing , activator (genetics) , microbiology and biotechnology , transcriptional regulation , biology , gene , gene expression , genetics , linguistics , philosophy
The zinc finger protein RE‐1 silencing transcription factor (REST) is a transcriptional repressor that represses neuronal genes in non‐neuronal tissues. We have analyzed the ability of REST and the REST mutants, RESTΔN and RESTΔC lacking either the N‐terminal or C‐terminal repression domains of REST, to inhibit transcription mediated by distinct transcriptional activator proteins. For this purpose we have designed an activator specific assay where transcription is activated as a result of only one distinct activation domain. In addition, binding sites for REST were inserted in the 5′‐untranslated region or at a distant position downstream of the polyadenylation signal. The results show that REST or the REST mutants containing only one repression domain were able to block transcriptional activation mediated by the transcriptional activation domains derived from p53, AP2, Egr‐1, and GAL4. Moreover, REST, as well as the REST mutants, blocked the activity of the phosphorylation‐dependent activation domain of Elk1. However, the activity of the activation domain derived from cAMP response element binding protein 2 (CREB2), was not inhibited by REST, RESTΔN or RESTΔC, suggesting that REST is able to distinguish between distinct transcriptional activation domains. Additionally, the activator specific assay, together with a positive‐dominant mutant of REST that activated instead of repressed transcription, was used in titration experiments to show that REST has transcriptional repression and no transcriptional activation properties when bound to the 5′‐untranslated region of a gene.