The repressor element silencing transcription factor (REST)-mediated transcriptional repression requires the inhibition of Sp1.

Details

Serval ID
serval:BIB_5233C37B0D56
Type
Article: article from journal or magazin.
Collection
Publications
Title
The repressor element silencing transcription factor (REST)-mediated transcriptional repression requires the inhibition of Sp1.
Journal
Journal of Biological Chemistry
Author(s)
Plaisance V., Niederhauser G., Azzouz F., Lenain V., Haefliger J.A., Waeber G., Abderrahmani A.
ISSN
0021-9258
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
280
Number
1
Pages
401-407
Language
english
Notes
Publication types: Journal Article
Abstract
The terminal differentiation of neuronal and pancreatic beta-cells requires the specific expression of genes that are targets of an important transcriptional repressor named RE-1 silencing transcription factor (REST). The molecular mechanism by which these REST target genes are expressed only in neuronal and beta-cells and are repressed by REST in other tissues is a central issue in differentiation program of neuronal and beta-cells. Herein, we showed that the transcriptional factor Sp1 was required for expression of most REST target genes both in insulin-secreting cells and neuronal-like cells where REST is absent. Inhibition of REST in a non-beta and a non-neuronal cell model restored the transcriptional activity of Sp1. This activity was also restored by trichostatin A indicating the requirement of histone deacetylases for the REST-mediated silencing of Sp1. Conversely, exogenous introduction of REST blocked Sp1-mediated transcriptional activity. The REST inhibitory effect was mediated through its C-terminal repressor domain, which could interact with Sp1. Taken together, these data show that the inhibition of Sp1 by REST is required for the silencing of its target genes expression in non-neuronal and in non-beta-cells. We conclude that the interplay between REST and Sp1 determines the cell-specific expression of REST target genes.
Keywords
Animals, Cell Differentiation/genetics, Gene Expression Regulation, Gene Silencing, Hela Cells, Humans, Islets of Langerhans/cytology, Islets of Langerhans/physiology, Mice, Neurons/cytology, Neurons/physiology, PC12 Cells, Rats, Repressor Proteins/genetics, Sp1 Transcription Factor/antagonists & inhibitors, Sp1 Transcription Factor/genetics, Transcription Factors/genetics, Transcription, Genetic
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:16
Last modification date
20/08/2019 15:07
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