The N-terminal DNA-binding 'zinc finger' of the oestrogen and glucocorticoid receptors determines target gene specificity.

Détails

ID Serval
serval:BIB_4773D5D43A3B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The N-terminal DNA-binding 'zinc finger' of the oestrogen and glucocorticoid receptors determines target gene specificity.
Périodique
EMBO Journal
Auteur(s)
Green S., Kumar V., Theulaz I., Wahli W., Chambon P.
ISSN
0261-4189[print], 0261-4189[linking]
Statut éditorial
Publié
Date de publication
10/1988
Volume
7
Numéro
10
Pages
3037-3044
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Steroid hormone receptors activate specific gene transcription by binding as hormone-receptor complexes to short DNA enhancer-like elements termed hormone response elements (HREs). We have shown previously that a highly conserved 66 amino acid region of the oestrogen (ER) and glucocorticoid (GR) receptors, which corresponds to part of the receptor DNA binding domain (region C) is responsible for determining the specificity of target gene activation. This region contains two sub-regions (CI and CII) analogous to the 'zinc-fingers' of the transcription factor TFIIIA. We show here that CI and CII appear to be separate domains both involved in DNA binding. Furthermore, using chimaeric ERs in which either the first (N-terminal) (CI) or second (CII) 'zinc finger' region has been exchanged with that of the GR, indicates that it is the first 'zinc finger' which largely determines target gene specificity. We suggest that receptor recognition of the HRE is analogous to that of the helix-turn-helix DNA binding motif in that the receptor binds to DNA as a dimer with the first 'zinc finger' lying in the major groove recognizing one half of the palindromic HRE, and that protein-DNA interaction is stabilized through non-specific DNA binding and dimer interactions contributed by the second 'zinc finger'.
Mots-clé
Amino Acid Sequence, DNA Mutational Analysis, DNA-Binding Proteins/physiology, DNA-Binding Proteins/ultrastructure, Gene Expression Regulation, Histidine, Humans, Metalloproteins/physiology, Molecular Sequence Data, Receptors, Estrogen/physiology, Receptors, Estrogen/ultrastructure, Receptors, Glucocorticoid/physiology, Receptors, Glucocorticoid/ultrastructure, Regulatory Sequences, Nucleic Acid, Structure-Activity Relationship, Transcription Factors/physiology, Transcription, Genetic, Transcriptional Activation
Pubmed
Web of science
Création de la notice
24/01/2008 17:05
Dernière modification de la notice
03/03/2018 16:50
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