Linked Life Data

7737997

Source:http://linkedlifedata.com/resource/pubmed/id/7737997

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
1995-6-5
pubmed:abstractText
We investigated the molecular mechanisms underlying the transcriptional silencing and the hormone-induced activation of target genes by thyroid hormone receptor beta (TR-beta). We developed a cell-free transcription system containing HeLa cell nuclear extracts in which unliganded human TR-beta represses basal transcription from a promoter bearing thyroid hormone response elements. Binding of hormonal ligand to the receptor reverse this transcriptional silencing. Specific binding of TR-beta to the thyroid hormone response element at the target promoter is crucial for silencing. Studies employing TR-beta mutants indicate that the silencing activity is located within the C-terminal rather than the N-terminal domain of the receptor. Our studies reveal further that unliganded TR-beta inhibits the assembly of a functional transcription preinitiation complex (PIC) at the target promoter. We postulate that interaction with TR-beta impairs the function(s) of one or more assembling transcriptional complexes during the multistep assembly of a PIC. Consistent with this hypothesis, we observe that, in the absence of thyroid hormone, TR-beta or a heterodimer of TR-beta and retinoid-X-receptor undergoes direct protein-protein interactions with the transcription factor IIB-TATA binding protein complex, an early intermediate during PIC assembly. Binding of hormone to TR-beta dramatically reduces the interaction between the receptor and the transcription factor IIB-TATA binding protein complex. We propose that the role of ligand is to facilitate the assembly of functional PICs at the target promoter by reducing nonproductive interactions between TR-beta and the initiation factors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10601-11
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed-meshheading:7737997-Base Sequence, pubmed-meshheading:7737997-DNA-Binding Proteins, pubmed-meshheading:7737997-Gene Expression Regulation, pubmed-meshheading:7737997-HeLa Cells, pubmed-meshheading:7737997-Humans, pubmed-meshheading:7737997-Ligands, pubmed-meshheading:7737997-Macromolecular Substances, pubmed-meshheading:7737997-Molecular Sequence Data, pubmed-meshheading:7737997-Oligodeoxyribonucleotides, pubmed-meshheading:7737997-Receptors, Thyroid Hormone, pubmed-meshheading:7737997-Signal Transduction, pubmed-meshheading:7737997-TATA Box, pubmed-meshheading:7737997-TATA-Box Binding Protein, pubmed-meshheading:7737997-Transcription, Genetic, pubmed-meshheading:7737997-Transcription Factor TFIIB, pubmed-meshheading:7737997-Transcription Factors, pubmed-meshheading:7737997-Triiodothyronine
pubmed:year
1995
pubmed:articleTitle
Ligand modulates the interaction of thyroid hormone receptor beta with the basal transcription machinery.
pubmed:affiliation
Population Council, New York, New York 10021, USA.
pubmed:publicationType
Journal Article