The transcriptional repressor REST determines the cell-specific expression of the human MAPK8IP1 gene encoding IB1 (JIP-1).

Détails

ID Serval
serval:BIB_54A98A734031
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The transcriptional repressor REST determines the cell-specific expression of the human MAPK8IP1 gene encoding IB1 (JIP-1).
Périodique
Molecular and cellular biology
Auteur(s)
Abderrahmani A., Steinmann M., Plaisance V., Niederhauser G., Haefliger J.A., Mooser V., Bonny C., Nicod P., Waeber G.
ISSN
0270-7306
Statut éditorial
Publié
Date de publication
2001
Peer-reviewed
Oui
Volume
21
Numéro
21
Pages
7256-67
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
Islet-brain 1 (IB1) is the human and rat homologue of JIP-1, a scaffold protein interacting with the c-Jun amino-terminal kinase (JNK). IB1 expression is mostly restricted to the endocrine pancreas and to the central nervous system. Herein, we explored the transcriptional mechanism responsible for this preferential islet and neuronal expression of IB1. A 731-bp fragment of the 5' regulatory region of the human MAPK8IP1 gene was isolated from a human BAC library and cloned upstream of a luciferase reporter gene. This construct drove high transcriptional activity in both insulin-secreting and neuron-like cells but not in unrelated cell lines. Sequence analysis of this promoter region revealed the presence of a neuron-restrictive silencer element (NRSE) known to bind repressor zinc finger protein REST. This factor is not expressed in insulin-secreting and neuron-like cells. By mobility shift assay, we confirmed that REST binds to the NRSE present in the IB1 promoter. Once transiently transfected in beta-cell lines, the expression vector encoding REST repressed IB1 transcriptional activity. The introduction of a mutated NRSE in the 5' regulating region of the IB1 gene abolished the repression activity driven by REST in insulin-secreting beta cells and relieved the low transcriptional activity of IB1 observed in unrelated cells. Moreover, transfection in non-beta and nonneuronal cell lines of an expression vector encoding REST lacking its transcriptional repression domain relieved IB1 promoter activity. Last, the REST-mediated repression of IB1 could be abolished by trichostatin A, indicating that deacetylase activity is required to allow REST repression. Taken together, these data establish a critical role for REST in the control of the tissue-specific expression of the human IB1 gene.
Mots-clé
3T3 Cells, Adaptor Proteins, Signal Transducing, Animals, Base Sequence, Blotting, Northern, Carrier Proteins, DNA, Complementary, Enzyme Inhibitors, Gene Expression Regulation, Enzymologic, Gene Library, Hela Cells, Humans, Hydroxamic Acids, Mice, Molecular Sequence Data, Mutation, Neurons, PC12 Cells, Polymerase Chain Reaction, Promoter Regions, Genetic, RNA, Messenger, Rats, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection, Tumor Cells, Cultured, Zinc Fingers
Pubmed
Web of science
Open Access
Oui
Création de la notice
17/11/2008 9:57
Dernière modification de la notice
20/08/2019 15:09
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