Activation of myoD gene transcription by 3,5,3'-triiodo-L-thyronine: a direct role for the thyroid hormone and retinoid X receptors

Muscat, George E. O., Mynett-Johnson, Lesley, Dowhan, Dennis, Downes, Michael and Griggs, Russell (1994) Activation of myoD gene transcription by 3,5,3'-triiodo-L-thyronine: a direct role for the thyroid hormone and retinoid X receptors. Nucleic Acids Research, 22 4: 583-591. doi:10.1093/nar/22.4.583

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Author Muscat, George E. O.
Mynett-Johnson, Lesley
Dowhan, Dennis
Downes, Michael
Griggs, Russell
Title Activation of myoD gene transcription by 3,5,3'-triiodo-L-thyronine: a direct role for the thyroid hormone and retinoid X receptors
Journal name Nucleic Acids Research   Check publisher's open access policy
ISSN 0305-1048
Publication date 1994-02
Sub-type Article (original research)
DOI 10.1093/nar/22.4.583
Open Access Status DOI
Volume 22
Issue 4
Start page 583
End page 591
Total pages 9
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract
Thyroid hormones are major determinants of skeletal muscle differentiation In vivo. Triiodo-L-thyronlne treatment promotes terminal muscle differentiation and results In increased MyoD gene transcription in myogenic cell lines; furthermore myoD and fast myosln heavy chain gene expression are activated In rodent slow twitch muscle fibers (Molecular Endocrinology 6: 1185-1194, 1992; Development 118: 1137-1147, 1993). We have Identified a T3 response element (TRE) in the mouse MyoD promoter between nucleotide positions -337 and -309 (5' CTGAGGTCAGTACA-GGCTGGAGGAGTAGA 3'). This sequence conferred an appropriate T3 response to an enhanceriess SV40 promoter. In vitro binding studies showed that the thyroid hormone receptor {alpha} (TR{alpha}) formed a heterodimeric complex, with either the retinoid X receptor {alpha} or {gamma}1 isoforms (RXR {alpha}, RXR{gamma}), on the MyoD TRE that was specifically competed by other well characterised TREs and not by other response elements. Analyses of this heterodimer with a battery of steroid hormone response elements Indicated that the complex was efficiently competed by a direct repeat of the AGGTCA motif separated by 4 nucleotides as predicted by the 3-4-5 rule. EMSA experiments demonstrated that the nuclear factor(s) present In muscle cells that bound to the myoD TRE were constltutlvely expressed during myogenesis; this complex was competed by the myosin heavy chain, DR-4 and PAL-0 TREs in a sequence specific fashion. Western blot analysis Indicated that TR{alpha}1 was constitutively expressed during C2C12 differentiation. Mutagenesis of the myoD TRE indicated that the sequence of the direct repeats (AGGTCA) and the 4 nucleotide gap were necessary for efficient binding to the TR{alpha}/RXR{alpha} heterodimeric complex. In conclusion our data suggest that the TRE in the helix loop helix gene, myoD, is a target for the direct heterodimeric binding of TR{alpha} and RXR{alpha}/{gamma}. These results provide a molecular mechanism/model for the effects of triiodo-L-thyronine on In vitro myogenesis; the activation of myoD gene expression in the slow twitch fibres and the cascade of myogenic events regulated by thyroid hormone.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Diamantina Institute - Open Access Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 69 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 14 Jul 2010, 16:51:40 EST by Laura McTaggart on behalf of UQ Diamantina Institute