Disease relevance of LOC397942

• Chromatin disruption and histone acetylation in regulation of the human immunodeficiency virus type 1 long terminal repeat by thyroid hormone receptor [1].
• Cloning and expression of a thyroid hormone receptor alpha 1 in the perennibranchiate amphibian Proteus anguinus [2].

High impact information on LOC397942

• The association of thyroid hormone with the chromatin-bound TR/RXR heterodimer leads to the disruption of local chromatin structure in a transcription-independent process [3].
• Maximal transcriptional repression requires the presence of unliganded TR/RXR heterodimers during replication-coupled chromatin assembly [3].
• We establish that heterodimers of TR and 9-cis retinoic acid receptors (RXR) can bind to their recognition sites within chromatin both in vivo and in vitro and alternately repress or activate transcription dependent on the absence or presence of thyroid hormone [3].
• We have assembled the thyroid hormone-inducible promoter of the Xenopus thyroid hormone receptor (TR)beta A gene into chromatin using replication-coupled and -independent assembly pathways in vivo [3].
• A correlation of thyroid hormone receptor gene expression with amphibian metamorphosis [4].

Chemical compound and disease context of LOC397942

• We demonstrated the presence of thyroid hormone receptor alpha mRNAs in tissues of the perennibranchiate amphibian Proteus anguinus, which is insensitive to thyroid hormone [2].

Biological context of LOC397942

• They further provide the first example where TR is shown to mediate directly and sufficiently these developmental effects of T3 in individual organs by regulating target gene expression in these organs [5].
• Molecular analyses showed that dpTR induced metamorphosis by specifically binding to known T3 target genes, leading to increased local histone acetylation and gene activation, similar to T3-bound TR during natural metamorphosis [5].
• Whereas thyroid hormone receptor (TR) knockout and transgenic studies of mice have implicated TR involvement in mammalian development, the underlying molecular bases for the resulting phenotypes remain to be determined in vivo, especially considering that T3 is known to have both genomic, i.e., through TRs, and nongenomic effects on cells [5].
• Surprisingly, we found that SRC3 was recruited in a gene- and tissue-dependent manner to target genes by TR, both upon T3 treatment of premetamorphic tadpoles and during natural metamorphosis [6].
• By using the total dependence of amphibian metamorphosis on thyroid hormone (T3) as a model, we have investigated the role of steroid receptor coactivator 3 (SRC3) in gene activation by thyroid hormone receptor (TR) in vivo [6].

Anatomical context of LOC397942

• We used Xenopus oocytes to compare silencing effected by the thyroid hormone receptor (TR) and its mutated version, the oncoprotein v-ErbA, on partly and fully chromatinized TR-responsive templates in vivo [7].
• By inducing a dominant negative form of the thyroid hormone receptor under the control of doxycycline specifically in the nervous system we have delimited the developmental periods within which thyroid hormone controls innervation of the developing limb from the spinal cord [8].
• Transcription of both Xenopus thyroid hormone receptor (TR) genes, xTR alpha and -beta, is strongly up-regulated by their own ligand T3 during natural or T3-induced metamorphosis of tadpoles and in some Xenopus cell lines [9].
• Recent studies on metamorphosis have revealed the important role played by such processes as auto-and cross-regulation of thyroid hormone receptor (TR) genes and by cell death or apoptosis, as in the maturation of the central nervous system, tissue restructuring and organolysis [10].
• In an attempt to explain this potentiation, we find that T3 also upregulates thyroid hormone receptor beta, but not alpha, transcripts and rapidly enhances the autoinduction of estrogen receptor (ER) mRNA in adult Xenopus hepatocytes [11].

Associations of LOC397942 with chemical compounds

• Transgenic analysis reveals that thyroid hormone receptor is sufficient to mediate the thyroid hormone signal in frog metamorphosis [5].
• Tissue- and gene-specific recruitment of steroid receptor coactivator-3 by thyroid hormone receptor during development [6].
• Here we show that activation by androgen receptor and thyroid hormone receptor is associated with the promoter targeting of SRC family members, p300, SWI/SNF and the Mediator complex [12].
• Thyroid hormone receptor can modulate retinoic acid-mediated axis formation in frog embryogenesis [13].
• The addition of TR/retinoid X receptor together had no effect on the chromatin structure, but the inclusion of T(3) induced strong positioning of a dinucleosome in the TSH alpha proximal promoter that was bordered by regions that were hypersensitive to cleavage by methidiumpropyl EDTA [14].

Other interactions of LOC397942

• To test this hypothesis, we generated a Xenopus laevis TR beta mutant construct ineffective for gene repression owing to impaired corepressor NCoR recruitment [15].
• Thyroid hormone receptor acts as a hormone-dependent transcriptional transactivator and as a transcriptional repressor in the absence of thyroid hormone [13].
• Prolactin prevents the autoinduction of thyroid hormone receptor mRNAs during amphibian metamorphosis [16].

Analytical, diagnostic and therapeutic context of LOC397942

• Histone H1 association is without significant consequence for the binding of the heterodimer of thyroid hormone receptor and 9-cis retinoic acid receptor (TR/RXR) to nucleosomal DNA in vitro, or for the regulation of TRbetaA gene transcription following microinjection into the oocyte nucleus [17].
• Electrophoretic mobility shift assays with recombinant Xenopus TR alpha, TR beta, retinoid-X receptor-alpha (RXR alpha) and RXR gamma proteins showed that TR-RXR heterodimers, but not TR or RXR monomers or homodimers, strongly bound the natural and synthetic distal and proximal DR+4 elements in a ligand-independent manner [9].
• Using a combination of filter hybridization, RNase protection assay and in situ hybridization, we first show that very low doses (10(-9) M) of exogenous T3 will autoinduce thyroid hormone receptor (TR) mRNA in several tissues of premetamorphic tadpoles [18].
• We assessed the changes in steady-state mRNA levels of thyroid hormone receptor alpha- and beta-isoforms and the basic transcription element binding (BTEB) protein by quantitative real-time polymerase chain reaction [19].

References