Characterization of the thyroid hormone response element in the skeletal alpha-actin gene: negative regulation of T3 receptor binding by the retinoid X receptor.

Muscat G.E., Griggs R., Downes M. and Emery J. (1993) Characterization of the thyroid hormone response element in the skeletal alpha-actin gene: negative regulation of T3 receptor binding by the retinoid X receptor.. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, 4 4: 269-279.

Author Muscat G.E.
Griggs R.
Downes M.
Emery J.
Title Characterization of the thyroid hormone response element in the skeletal alpha-actin gene: negative regulation of T3 receptor binding by the retinoid X receptor.
Journal name Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research   Check publisher's open access policy
ISSN 1044-9523
Publication date 1993-01-01
Year available 1993
Sub-type Article (original research)
Open Access Status Not yet assessed
Volume 4
Issue 4
Start page 269
End page 279
Total pages 11
Place of publication PHILADELPHIA
Publisher AMER ASSOC CANCER RESEARCH
Language eng
Subject 1307 Cell Biology
1312 Molecular Biology
Abstract We have identified a T3 response element (TRE) in the human skeletal alpha-actin gene between nucleotide positions -273 and -249 (5' GGGCAACTGGGTCG-GGTCAGGAGGG 3') that is accommodated by the core receptor binding motif, A/G GG T/A C A/G. This sequence conferred appropriate hormonal regulation in a thyroid hormone receptor (TRalpha) dependent manner to an enhancerless SV40 promoter. Electrophoretic mobility shift assay experiments showed that Escherichia coli expressed and affinity purified TRalpha bound to the skeletal alpha-actin TRE in a sequence specific manner. The alpha-actin TRE bound TRalpha dimers cooperatively. Mutagenesis of the alpha-actin TRE indicated that the core binding motifs and the gap sequences were the most important for efficient binding to TRalpha. The retinoid X receptor alpha(RXRalpha) interacted with the alpha-actin TRE in a sequence specific fashion and formed heterodimeric complexes with TRalpha on the alpha-actin TRE. However, increased levels of RXRalpha decreased the binding of TRalpha to the alpha-actin TRE, in contrast to promoting TRalpha binding to the alpha-myosin heavy chain TRE. Furthermore, the alpha-actin, palindromic, synthetic direct repeat, alpha-myosin heavy chain, and growth hormone TREs interacted with an identical nuclear factor in vitro in muscle cells. In conclusion, our data suggest that the human skeletal alpha-actin TRE is a target for direct cross-talk between two different hormonal signals (T3 and 9-cis-retinoic acid) at the receptor level. To our knowledge, this is the first demonstration of homodimeric and heterodimeric binding of TRalpha and RXRalpha to a TRE in a gene expressed primarily in skeletal muscle.
Keyword Cell Biology
Cell Biology
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import - Archived
 
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