Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20226 (TATA-binding protein)
 1,297 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The thyroid hormone receptor (TR) belongs to the steroid/nuclear receptor superfamily of ligand-inducible transcription factors. Numerous studies using transient transfection assays have demonstrated that in the absence of thyroid hormone (T3), unliganded TR acts as a constitutive repressor of transcription on genes bearing TR-response elements. We examined the molecular mechanism of TR repression in vitro using both HeLa nuclear extracts and purified basal factors. Here, we show that unliganded TR is an active transcriptional repressor, distinct from passive repressors that compete with activators for DNA binding. Repression by TR can be relieved by adding the T3 analog triiodothyroactic acid, suggesting that liganded TR undergoes a conformational change that masks or disrupts the repressor function. Repression by TR is mediated through the basal transcription machinery and can occur independently of previously characterized TATA-binding protein-associated cofactors thought to be involved in either basal repression or activator-dependent transcription. TR inhibits transcription at an early step during preinitiation complex (PIC) assembly, as preassembled PICs are refractory to the inhibitory effects of TR.
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PMID:Unliganded thyroid hormone receptor inhibits formation of a functional preinitiation complex: implications for active repression. 839 77

Transcriptional coactivators play a crucial role in gene expression by communicating between regulatory factors and the basal transcription machinery. The coactivator multiprotein bridging factor 1 (MBF1) was originally identified as a bridging molecule that connects the Drosophila nuclear receptor FTZ-F1 and TATA-binding protein (TBP). The MBF1 sequence is highly conserved across species from Saccharomyces cerevisiae to human. Here we provide evidence acquired in vitro and in vivo that yeast MBF1 mediates GCN4-dependent transcriptional activation by bridging the DNA-binding region of GCN4 and TBP. These findings indicate that the coactivator MBF1 functions by recruiting TBP to promoters where DNA-binding regulators are bound.
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PMID:Yeast coactivator MBF1 mediates GCN4-dependent transcriptional activation. 971 May 80

The nuclear receptor hepatocyte nuclear factor 4 (HNF-4) is an important regulator of several genes involved in diverse metabolic and developmental pathways. Mutations in the HNF-4A gene are responsible for the maturity-onset diabetes of the young type 1. Recently, we showed that the 24 N-terminal residues of HNF-4 function as an acidic transcriptional activator, termed AF-1 (Hadzopoulou-Cladaras, M., Kistanova, E., Evagelopoulou, C., Zeng, S. , Cladaras C., and Ladias, J. A. A. (1997) J. Biol. Chem. 272, 539-550). To identify the critical residues for this activator, we performed an extensive genetic analysis using site-directed mutagenesis. We showed that the aromatic and bulky hydrophobic residues Tyr6, Tyr14, Phe19, Lys10, and Lys17 are essential for AF-1 function. To a lesser degree, five acidic residues are also important for optimal activity. Positional changes of Tyr6 and Tyr14 reduced AF-1 activity, underscoring the importance of primary structure for this activator. Our analysis also indicated that AF-1 is bipartite, consisting of two modules that synergize to activate transcription. More important, AF-1 shares common structural motifs and molecular targets with the activators of the tumor suppressor protein p53 and NF-kappaB-p65, suggesting similar mechanisms of action. Remarkably, AF-1 interacted specifically with multiple transcriptional targets, including the TATA-binding protein; the TATA-binding protein-associated factors TAFII31 and TAFII80; transcription factor IIB; transcription factor IIH-p62; and the coactivators cAMP-responsive element-binding protein-binding protein, ADA2, and PC4. The interaction of AF-1 with proteins that regulate distinct steps of transcription may provide a mechanism for synergistic activation of gene expression by AF-1.
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PMID:Critical structural elements and multitarget protein interactions of the transcriptional activator AF-1 of hepatocyte nuclear factor 4. 979 14

The action of oestrogen hormones is mediated through the oestrogen receptor (ER), a member of a large superfamily of nuclear receptors that function as ligand-activated transcription factors. Sequence-specific transcription factors, including the nuclear receptor superfamily, are thought to interact either directly or indirectly with general transcription factors to regulate transcription. Although numerous studies have focused on the identification of potential co-activators interacting with isolated trans-activation domains of ER, few have investigated the mechanisms by which ER transmits its signal to the basal transcription machinery. We show that ER does not stabilize the binding of the TATA-box binding protein (TBP) of the TFIID complex, or of TFIIB to the promoter, although a stable ER-TBP-TFIIB-promoter complex was detected, suggesting that ER, TBP and TFIIB might interact with each other to form a complex to the promoter. We also demonstrate that ER binds specifically to TFIIB, a key component of the preinitiation complex. Affinity chromatography with immobilized deletion mutants of ER maps a TFIIB interaction region that encompasses the DNA-binding domain. The addition of excess TFIIB to transcription reactions in vitro did not, however, affect the magnitude of transcriptional activation by ER. These results indicate that, in contrast with current models, ER does not activate transcription by increasing the rate of assembly of TFIIB into the transcription complex. An increased concentration of TFIIB was unable, by itself, to overcome the requirement for ER. By using an immobilized promoter-template assay employing nuclear extract from HeLa cells, recombinant human ER increased the stable association of subsequent components of the transcription machinery (TFIIE and TFIIF), in correlation with ER-induced transcription. Our results suggest that ER acts, in an early step, during or immediately after the formation of template-committed complexes containing TFIIB, favouring the recruitment of one or more components of the basic transcription machinery as well as co-activators.
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PMID:Oestrogen receptor facilitates the formation of preinitiation complex assembly: involvement of the general transcription factor TFIIB. 984 76

Multiple alternative interactions between activators and co-activators stimulate transcription by RNA polymerase II. In the past two years, multiprotein co-activator complexes have been characterized and their subunits defined. TATA-box binding protein associated factor (TAF) subunits of yeast TFIID were found to be generally required for transcription in vivo. Mammalian multisubunit coactivator complexes with homologs of the yeast SRB/Mediator subunits have been characterized. Structures of nuclear receptor-coactivator complexes have been determined.
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PMID:Activation of RNA polymerase II transcription. 1039 59

The state of chromatin (the packaging of DNA in eukaryotes) has long been recognized to have major effects on levels of gene expression, and numerous chromatin-altering strategies-including ATP-dependent remodeling and histone modification-are employed in the cell to bring about transcriptional regulation. Of these, histone acetylation is one of the best characterized, as recent years have seen the identification and further study of many histone acetyltransferase (HAT) proteins and their associated complexes. Interestingly, most of these proteins were previously shown to have coactivator or other transcription-related functions. Confirmed and putative HAT proteins have been identified from various organisms from yeast to humans, and they include Gcn5-related N-acetyltransferase (GNAT) superfamily members Gcn5, PCAF, Elp3, Hpa2, and Hat1: MYST proteins Sas2, Sas3, Esa1, MOF, Tip60, MOZ, MORF, and HBO1; global coactivators p300 and CREB-binding protein; nuclear receptor coactivators SRC-1, ACTR, and TIF2; TATA-binding protein-associated factor TAF(II)250 and its homologs; and subunits of RNA polymerase III general factor TFIIIC. The acetylation and transcriptional functions of these HATs and the native complexes containing them (such as yeast SAGA, NuA4, and possibly analogous human complexes) are discussed. In addition, some of these HATs are also known to modify certain nonhistone transcription-related proteins, including high-mobility-group chromatin proteins, activators such as p53, coactivators, and general factors. Thus, we also detail these known factor acetyltransferase (FAT) substrates and the demonstrated or potential roles of their acetylation in transcriptional processes.
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PMID:Acetylation of histones and transcription-related factors. 1083 22

The transcription factor TFIID consists of TATA-binding protein (TBP) and TBP-associated factors (TAFs). TAFs are essential for modulation of transcriptional activity but the regulation of TAFs is complex and many important aspects remain unclear. In this study, we have identified and characterized five novel truncated forms of the TFIID subunit TAF4 (TAF(II)135). Analysis of the mouse gene structure revealed that all truncations were the results of alternative splicing and resulted in the loss of domains or parts of domains implicated in TAF4 functional interactions. Results from transcriptional assays showed that several of the TAF4 isoforms exerted dominant negative effects on TAF4 activity in nuclear receptor-mediated transcriptional activation. In addition, alternative TAF4 isoforms could be detected in specific cell types. Our results indicate an additional level of complexity in TAF4-mediated regulation of transcription and suggest context-specific roles for these new TAF4 isoforms in transcriptional regulation in vivo.
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PMID:Novel isoforms of the TFIID subunit TAF4 modulate nuclear receptor-mediated transcriptional activity. 1553 Apr 31