This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Buchholz, D. R. Articles by Shi, Y.-B. Search for Related Content PubMed PubMed Citation Articles by Buchholz, D. R. Articles by Shi, Y.-B.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 2003, p. 6750-6758, Vol. 23, No. 19
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.19.6750-6758.2003

A Dominant-Negative Thyroid Hormone Receptor Blocks Amphibian Metamorphosis by Retaining Corepressors at Target Genes

Unit on Molecular Morphogenesis, Laboratory of Gene Regulation and Development, National Institute for Child Health and Human Development, Bethesda, Maryland 20892-5431

Received 22 April 2003/ Returned for modification 17 June 2003/ Accepted 26 June 2003

The total dependence of amphibian metamorphosis on thyroid hormone (T₃) provides a unique vertebrate model for studying the molecular mechanism of T₃ receptor (TR) function in vivo. In vitro transcription and developmental expression studies have led to a dual function model for TR in amphibian development, i.e., TRs act as transcriptional repressors in premetamorphic tadpoles and as activators during metamorphosis. We examined molecular mechanisms of TR action in T3-induced metamorphosis by using dominant-negative receptors (dnTR) ubiquitously expressed in transgenic Xenopus laevis. We showed that T₃-induced activation of T₃ target genes and morphological changes are blocked in dnTR transgenic animals. By using chromatin immunoprecipitation, we show that dnTR bound to target promoters, which led to retention of corepressors and continued histone deacetylation in the presence of T₃. These results thus provide direct in vivo evidence for the first time for a molecular mechanism of altering gene expression by a dnTR. The correlation between dnTR-mediated gene repression and inhibition of metamorphosis also supports a key aspect of the dual function model for TR in development: during T₃-induced metamorphosis, TR functions as an activator via release of corepressors and promotion of histone acetylation and gene activation.

This article has been cited by other articles:

• Heimeier, R. A., Hsia, V. S., Shi, Y.-B. (2008). Participation of Brahma-Related Gene 1 (BRG1)-Associated Factor 57 and BRG1-Containing Chromatin Remodeling Complexes in Thyroid Hormone-Dependent Gene Activation during Vertebrate Development. Mol. Endocrinol. 22: 1065-1077 [Abstract] [Full Text]  
• Matsuda, H., Paul, B. D., Choi, C. Y., Shi, Y.-B. (2007). Contrasting Effects of Two Alternative Splicing Forms of Coactivator-Associated Arginine Methyltransferase 1 on Thyroid Hormone Receptor-Mediated Transcription in Xenopus laevis. Mol. Endocrinol. 21: 1082-1094 [Abstract] [Full Text]  
• Paul, B. D., Buchholz, D. R., Fu, L., Shi, Y.-B. (2007). SRC-p300 Coactivator Complex Is Required for Thyroid Hormone-induced Amphibian Metamorphosis. J. Biol. Chem. 282: 7472-7481 [Abstract] [Full Text]  
• Fu, L., Tomita, A., Wang, H., Buchholz, D. R., Shi, Y.-B. (2006). Transcriptional Regulation of the Xenopus laevis Stromelysin-3 Gene by Thyroid Hormone Is Mediated by a DNA Element in the First Intron. J. Biol. Chem. 281: 16870-16878 [Abstract] [Full Text]  
• Nygard, M., Becker, N., Demeneix, B., Pettersson, K., Bondesson, M. (2006). Thyroid hormone-mediated negative transcriptional regulation of Necdin expression.. J Mol Endocrinol 36: 517-530 [Abstract] [Full Text]  
• Buchholz, D. R., Paul, B. D., Shi, Y.-B. (2005). Gene-specific Changes in Promoter Occupancy by Thyroid Hormone Receptor during Frog Metamorphosis: IMPLICATIONS FOR DEVELOPMENTAL GENE REGULATION. J. Biol. Chem. 280: 41222-41228 [Abstract] [Full Text]  
• Fu, L., Ishizuya-Oka, A., Buchholz, D. R., Amano, T., Matsuda, H., Shi, Y.-B. (2005). A Causative Role of Stromelysin-3 in Extracellular Matrix Remodeling and Epithelial Apoptosis during Intestinal Metamorphosis in Xenopus laevis. J. Biol. Chem. 280: 27856-27865 [Abstract] [Full Text]  
• Paul, B. D., Buchholz, D. R., Fu, L., Shi, Y.-B. (2005). Tissue- and Gene-specific Recruitment of Steroid Receptor Coactivator-3 by Thyroid Hormone Receptor during Development. J. Biol. Chem. 280: 27165-27172 [Abstract] [Full Text]  
• Paul, B. D., Fu, L., Buchholz, D. R., Shi, Y.-B. (2005). Coactivator Recruitment Is Essential for Liganded Thyroid Hormone Receptor To Initiate Amphibian Metamorphosis. Mol. Cell. Biol. 25: 5712-5724 [Abstract] [Full Text]  
• Angelin-Duclos, C., Domenget, C., Kolbus, A., Beug, H., Jurdic, P., Samarut, J. (2005). Thyroid hormone T3 acting through the thyroid hormone {alpha} receptor is necessary for implementation of erythropoiesis in the neonatal spleen environment in the mouse. Development 132: 925-934 [Abstract] [Full Text]  
• Buchholz, D. R., Tomita, A., Fu, L., Paul, B. D., Shi, Y.-B. (2004). Transgenic Analysis Reveals that Thyroid Hormone Receptor Is Sufficient To Mediate the Thyroid Hormone Signal in Frog Metamorphosis. Mol. Cell. Biol. 24: 9026-9037 [Abstract] [Full Text]  
• Tomita, A., Buchholz, D. R., Shi, Y.-B. (2004). Recruitment of N-CoR/SMRT-TBLR1 Corepressor Complex by Unliganded Thyroid Hormone Receptor for Gene Repression during Frog Development. Mol. Cell. Biol. 24: 3337-3346 [Abstract] [Full Text]