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

Antonella Farsetti, Tomoaki Mitsuhashi, Beatrice Desvergne, Jacob Robbins, Vera M. Nikodem

Research output: Contribution to journalArticle

Abstract

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 α, 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 TRα, 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.

Original languageEnglish
Pages (from-to)23226-23232
Number of pages7
JournalJournal of Biological Chemistry
Volume266
Issue number34
Publication statusPublished - Dec 5 1991

Fingerprint

Myelin Basic Protein
Thyroid Hormones
Gene expression
Rodentia
Brain
Gene Expression
Genes
Chloramphenicol O-Acetyltransferase
Triiodothyronine
Assays
Spodoptera
Thyroid Hormone Receptors
Messenger RNA
Baculoviridae
Transcription
Ribonucleases
Thyroxine
Genetic Promoter Regions
Transfection
Rats

ASJC Scopus subject areas

  • Biochemistry

Cite this

Farsetti, A., Mitsuhashi, T., Desvergne, B., Robbins, J., & Nikodem, V. M. (1991). Molecular basis of thyroid hormone regulation of myelin basic protein gene expression in rodent brain. Journal of Biological Chemistry, 266(34), 23226-23232.

Molecular basis of thyroid hormone regulation of myelin basic protein gene expression in rodent brain. / Farsetti, Antonella; Mitsuhashi, Tomoaki; Desvergne, Beatrice; Robbins, Jacob; Nikodem, Vera M.

In: Journal of Biological Chemistry, Vol. 266, No. 34, 05.12.1991, p. 23226-23232.

Research output: Contribution to journalArticle

Farsetti, A, Mitsuhashi, T, Desvergne, B, Robbins, J & Nikodem, VM 1991, 'Molecular basis of thyroid hormone regulation of myelin basic protein gene expression in rodent brain', Journal of Biological Chemistry, vol. 266, no. 34, pp. 23226-23232.
Farsetti A, Mitsuhashi T, Desvergne B, Robbins J, Nikodem VM. Molecular basis of thyroid hormone regulation of myelin basic protein gene expression in rodent brain. Journal of Biological Chemistry. 1991 Dec 5;266(34):23226-23232.
Farsetti, Antonella ; Mitsuhashi, Tomoaki ; Desvergne, Beatrice ; Robbins, Jacob ; Nikodem, Vera M. / Molecular basis of thyroid hormone regulation of myelin basic protein gene expression in rodent brain. In: Journal of Biological Chemistry. 1991 ; Vol. 266, No. 34. pp. 23226-23232.
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