Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract??? Thyroid hormone receptors (TRs) can repress or activate target genes depending on the absence or presence of thyroid hormone (T3), respectively. This hormone-dependent gene regulation is mediated by recruitment of co-repressors in the absence of T3 and coactivators in its presence. Many TR-interacting coactivators have been characterized in vitro. In comparison, few studies have addressed the developmental roles of these cofactors in vivo. We have investigated the role of coactivators in transcriptional activation by TR during postembryonic tissue remodeling by using amphibian metamorphosis as a model system. We have previously shown that steroid receptor coactivator 3 (SRC3) is expressed and upregulated during metamorphosis, suggesting a role in gene regulation by liganded TR. Here, we have generated transgenic tadpoles expressing a dominant negative form of SRC3 (F-dnSRC3). The transgenic tadpoles exhibited normal growth and development throughout embryogenesis and premetamorphic stages. However, transgenic expression of F-dnSRC3 inhibits essentially all aspects of T3-induced metamorphosis, as well as natural metamorphosis, leading to delayed or arrested metamorphosis or the formation of tailed frogs. Molecular analysis revealed that F-dnSRC3 functioned by blocking the recruitment of endogenous coactivators to T3 target genes without affecting corepressor release, thereby preventing the T3-dependent gene regulation program responsible for tissue transformations during metamorphosis. Our studies thus demonstrate that coactivator recruitment, aside from corepressor release, is required for T3 function in development and further provide the first example where a specific coactivator-dependent gene regulation pathway by a nuclear receptor has been shown to underlie specific developmental events.
Amano,
Thyroid hormone regulation of a transcriptional coactivator in Xenopus laevis: implication for a role in postembryonic tissue remodeling.
2002, Pubmed,
Xenbase
Amano,
Thyroid hormone regulation of a transcriptional coactivator in Xenopus laevis: implication for a role in postembryonic tissue remodeling.
2002,
Pubmed
,
Xenbase
Buchholz,
A dominant-negative thyroid hormone receptor blocks amphibian metamorphosis by retaining corepressors at target genes.
2003,
Pubmed
,
Xenbase
Buchholz,
Transgenic analysis reveals that thyroid hormone receptor is sufficient to mediate the thyroid hormone signal in frog metamorphosis.
2004,
Pubmed
,
Xenbase
Burrow,
Maternal and fetal thyroid function.
1994,
Pubmed
Carswell,
Efficiency of utilization of the simian virus 40 late polyadenylation site: effects of upstream sequences.
1989,
Pubmed
Chen,
Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300.
1997,
Pubmed
Chen,
A transcriptional co-repressor that interacts with nuclear hormone receptors.
1995,
Pubmed
Chubet,
Vectors for expression and secretion of FLAG epitope-tagged proteins in mammalian cells.
1996,
Pubmed
Damjanovski,
Function of thyroid hormone receptors during amphibian development.
2002,
Pubmed
,
Xenbase
Davis,
Nongenomic actions of thyroid hormone.
1996,
Pubmed
Ding,
Nuclear receptor-binding sites of coactivators glucocorticoid receptor interacting protein 1 (GRIP1) and steroid receptor coactivator 1 (SRC-1): multiple motifs with different binding specificities.
1998,
Pubmed
Feng,
Hormone-dependent coactivator binding to a hydrophobic cleft on nuclear receptors.
1998,
Pubmed
Feng,
Transgenic targeting of a dominant negative corepressor to liver blocks basal repression by thyroid hormone receptor and increases cell proliferation.
2001,
Pubmed
Flamant,
Thyroid hormone receptors: lessons from knockout and knock-in mutant mice.
2003,
Pubmed
Forrest,
Recessive resistance to thyroid hormone in mice lacking thyroid hormone receptor beta: evidence for tissue-specific modulation of receptor function.
1996,
Pubmed
Fraichard,
The T3R alpha gene encoding a thyroid hormone receptor is essential for post-natal development and thyroid hormone production.
1997,
Pubmed
Fu,
Novel double promoter approach for identification of transgenic animals: A tool for in vivo analysis of gene function and development of gene-based therapies.
2002,
Pubmed
,
Xenbase
Furlow,
In vitro and in vivo analysis of the regulation of a transcription factor gene by thyroid hormone during Xenopus laevis metamorphosis.
1999,
Pubmed
,
Xenbase
Gauthier,
Different functions for the thyroid hormone receptors TRalpha and TRbeta in the control of thyroid hormone production and post-natal development.
1999,
Pubmed
Gehin,
The function of TIF2/GRIP1 in mouse reproduction is distinct from those of SRC-1 and p/CIP.
2002,
Pubmed
Guenther,
A core SMRT corepressor complex containing HDAC3 and TBL1, a WD40-repeat protein linked to deafness.
2000,
Pubmed
Göthe,
Mice devoid of all known thyroid hormone receptors are viable but exhibit disorders of the pituitary-thyroid axis, growth, and bone maturation.
1999,
Pubmed
Heery,
A signature motif in transcriptional co-activators mediates binding to nuclear receptors.
1997,
Pubmed
Hong,
GRIP1, a novel mouse protein that serves as a transcriptional coactivator in yeast for the hormone binding domains of steroid receptors.
1996,
Pubmed
Hörlein,
Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor.
1995,
Pubmed
Ishizuka,
The N-CoR/histone deacetylase 3 complex is required for repression by thyroid hormone receptor.
2003,
Pubmed
Ishizuya-Oka,
Requirement for matrix metalloproteinase stromelysin-3 in cell migration and apoptosis during tissue remodeling in Xenopus laevis.
2000,
Pubmed
,
Xenbase
Ishizuya-Oka,
Thyroid-hormone-dependent and fibroblast-specific expression of BMP-4 correlates with adult epithelial development during amphibian intestinal remodeling.
2001,
Pubmed
,
Xenbase
Ito,
Involvement of the TRAP220 component of the TRAP/SMCC coactivator complex in embryonic development and thyroid hormone action.
2000,
Pubmed
Ito,
The TRAP/SMCC/Mediator complex and thyroid hormone receptor function.
2001,
Pubmed
Jepsen,
Combinatorial roles of the nuclear receptor corepressor in transcription and development.
2000,
Pubmed
Jones,
N-CoR-HDAC corepressor complexes: roles in transcriptional regulation by nuclear hormone receptors.
2003,
Pubmed
,
Xenbase
Kim,
Molecular cloning of xSRC-3, a novel transcription coactivator from Xenopus, that is related to AIB1, p/CIP, and TIF2.
1998,
Pubmed
,
Xenbase
Kroll,
Transgenic Xenopus embryos from sperm nuclear transplantations reveal FGF signaling requirements during gastrulation.
1996,
Pubmed
,
Xenbase
LaFranchi,
Thyroid function in the preterm infant.
1999,
Pubmed
Lazar,
Thyroid hormone receptors: multiple forms, multiple possibilities.
1993,
Pubmed
Li,
RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2.
1997,
Pubmed
Li,
Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3.
2000,
Pubmed
,
Xenbase
Mangelsdorf,
The nuclear receptor superfamily: the second decade.
1995,
Pubmed
Metz,
Structural and functional analysis of the BMP-4 promoter in early embryos of Xenopus laevis.
1998,
Pubmed
,
Xenbase
Nolte,
Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma.
1998,
Pubmed
Oñate,
Sequence and characterization of a coactivator for the steroid hormone receptor superfamily.
1995,
Pubmed
Patterton,
Transcriptional activation of the matrix metalloproteinase gene stromelysin-3 coincides with thyroid hormone-induced cell death during frog metamorphosis.
1995,
Pubmed
,
Xenbase
Paul,
Distinct expression profiles of transcriptional coactivators for thyroid hormone receptors during Xenopus laevis metamorphosis.
2003,
Pubmed
,
Xenbase
Rachez,
Mediator complexes and transcription.
2001,
Pubmed
Ranjan,
Transcriptional repression of Xenopus TR beta gene is mediated by a thyroid hormone response element located near the start site.
1994,
Pubmed
,
Xenbase
Sachs,
Involvement of histone deacetylase at two distinct steps in gene regulation during intestinal development in Xenopus laevis.
2001,
Pubmed
,
Xenbase
Sachs,
An essential role of histone deacetylases in postembryonic organ transformations in Xenopus laevis.
2001,
Pubmed
,
Xenbase
Sachs,
Dual functions of thyroid hormone receptors during Xenopus development.
2000,
Pubmed
,
Xenbase
Sachs,
Targeted chromatin binding and histone acetylation in vivo by thyroid hormone receptor during amphibian development.
2000,
Pubmed
,
Xenbase
Sachs,
Nuclear receptor corepressor recruitment by unliganded thyroid hormone receptor in gene repression during Xenopus laevis development.
2002,
Pubmed
,
Xenbase
Schreiber,
Diverse developmental programs of Xenopus laevis metamorphosis are inhibited by a dominant negative thyroid hormone receptor.
2001,
Pubmed
,
Xenbase
Shi,
Biphasic intestinal development in amphibians: embryogenesis and remodeling during metamorphosis.
1996,
Pubmed
,
Xenbase
Shi,
Cloning and characterization of the ribosomal protein L8 gene from Xenopus laevis.
1994,
Pubmed
,
Xenbase
Shiau,
The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen.
1998,
Pubmed
Stolow,
Xenopus sonic hedgehog as a potential morphogen during embryogenesis and thyroid hormone-dependent metamorphosis.
1995,
Pubmed
,
Xenbase
Takeshita,
TRAM-1, A novel 160-kDa thyroid hormone receptor activator molecule, exhibits distinct properties from steroid receptor coactivator-1.
1997,
Pubmed
Tata,
Gene expression during metamorphosis: an ideal model for post-embryonic development.
1993,
Pubmed
Tomita,
Fusion protein of retinoic acid receptor alpha with promyelocytic leukemia protein or promyelocytic leukemia zinc finger protein recruits N-CoR-TBLR1 corepressor complex to repress transcription in vivo.
2003,
Pubmed
,
Xenbase
Tomita,
Recruitment of N-CoR/SMRT-TBLR1 corepressor complex by unliganded thyroid hormone receptor for gene repression during frog development.
2004,
Pubmed
,
Xenbase
Torchia,
The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function.
1997,
Pubmed
Tsai,
Molecular mechanisms of action of steroid/thyroid receptor superfamily members.
1994,
Pubmed
Voegel,
The coactivator TIF2 contains three nuclear receptor-binding motifs and mediates transactivation through CBP binding-dependent and -independent pathways.
1998,
Pubmed
Voegel,
TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors.
1996,
Pubmed
Wang,
Regulation of somatic growth by the p160 coactivator p/CIP.
2000,
Pubmed
Wikström,
Abnormal heart rate and body temperature in mice lacking thyroid hormone receptor alpha 1.
1998,
Pubmed
Wong,
Coordinated regulation of and transcriptional activation by Xenopus thyroid hormone and retinoid X receptors.
1995,
Pubmed
,
Xenbase
Xu,
The steroid receptor coactivator SRC-3 (p/CIP/RAC3/AIB1/ACTR/TRAM-1) is required for normal growth, puberty, female reproductive function, and mammary gland development.
2000,
Pubmed
Yao,
Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300.
1998,
Pubmed
Yaoita,
Xenopus laevis alpha and beta thyroid hormone receptors.
1990,
Pubmed
,
Xenbase
Yen,
Physiological and molecular basis of thyroid hormone action.
2001,
Pubmed
Yoon,
Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1 and TBLR1.
2003,
Pubmed
Yoshizato,
Biochemistry and cell biology of amphibian metamorphosis with a special emphasis on the mechanism of removal of larval organs.
1989,
Pubmed
Zhang,
The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2.
2002,
Pubmed
Zhang,
The mechanism of action of thyroid hormones.
2000,
Pubmed
