Molecular basis of thyroid hormone regulation of myelin basic protein gene expression in rodent brain.

Détails

ID Serval
serval:BIB_C539B8C46ADB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Molecular basis of thyroid hormone regulation of myelin basic protein gene expression in rodent brain.
Périodique
Journal of Biological Chemistry
Auteur(s)
Farsetti A., Mitsuhashi T., Desvergne B., Robbins J., Nikodem V.M.
ISSN
0021-9258
Statut éditorial
Publié
Date de publication
12/1991
Peer-reviewed
Oui
Volume
266
Numéro
34
Pages
23226-23232
Langue
anglais
Résumé
Regulation of myelin basic protein (MBP) gene expression by thyroid hormone has been investigated in rodent brain. Quantitation of the 4 major alternatively spliced transcripts by RNase protection assay showed that the individual mRNAs, corresponding to MBP isoforms 21.5, 18.5, 17, and 14 kDa, were decreased from 2- to 17-fold at all ages studied (4-60 days) in hypothyroid animals when compared to euthyroid, but the timing of onset of expression was not altered. MBP mRNA was also reduced in young adult rats thyroidectomized at the age of 5-6 weeks and was restored to normal by thyroxine administration. Nuclear run-off assays showed that the rate of MBP gene transcription is dependent on thyroid state. Co-transfection of MBP (-256/+1)-chloramphenicol acetyltransferase chimeric gene with a plasmid expressing thyroid hormone receptor alpha, and in the presence of 3,5,3'-triiodothyronine, into NIH3T3 or NG108-15, increased chloramphenicol acetyltransferase expression 4-fold. Using a footprinting technique and Spodoptera frugiperda 9 (Sf9) nuclear extract infected with baculovirus expressing TR alpha, we have identified a single DNA-binding site (-186/-163) for the receptor. A part of this region contains the AGGACA sequence found in thyroid hormone-responsive elements of other 3,5,3'-triiodothyronine-regulated genes. Our finding of a specific hormone-receptor interaction with the MBP promoter region is the first direct demonstration of a thyroid hormone-responsive element in a brain-specific gene.
Mots-clé
Animals, Base Sequence, Brain/metabolism, DNA/metabolism, Deoxyribonuclease I/metabolism, Gene Expression Regulation, Hypothyroidism/genetics, Male, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Myelin Basic Proteins/genetics, RNA, Messenger/metabolism, Rats, Rats, Inbred Strains, Receptors, Thyroid Hormone/metabolism, Regulatory Sequences, Nucleic Acid, Thyroid Hormones/physiology, Thyroxine/physiology, Transcription, Genetic, Triiodothyronine/physiology
Pubmed
Web of science
Création de la notice
24/01/2008 16:27
Dernière modification de la notice
20/08/2019 16:40
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