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

Autosomal dominant spinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders clinically characterized by late-onset ataxia and variable other manifestations. Genetically and clinically, SCA is highly heterogeneous. Recently, CAG repeat expansions in the gene encoding TATA-binding protein (TBP) have been found in a new form of SCA, which has been designated SCA17. To estimate the frequency of SCA17 among white SCA patients and to define the phenotypic variability, we determined the frequency of SCA17 in a large sample of 1,318 SCA patients. In total, 15 patients in four autosomal dominant SCA families had CAG/CAA repeat expansions in the TBP gene ranging from 45 to 54 repeats. The clinical features of our SCA17 patients differ from other SCA types by manifesting with psychiatric abnormalities and dementia. The neuropathology of SCA17 can be classified as a "pure cerebellar" or "cerebello-olivary" form of ataxia. However, intranuclear neuronal inclusion bodies with immunoreactivity to anti-TBP and antipolyglutamine were much more widely distributed throughout the brain gray matter than in other SCAs. Based on clinical and genetic data, we conclude that SCA17 is rare among white SCA patients. SCA17 should be considered in sporadic and familial cases of ataxia with accompanying psychiatric symptoms and dementia.
Ann Neurol 2003 Sep
PMID:Clinical features and neuropathology of autosomal dominant spinocerebellar ataxia (SCA17). 1295 69

Glucose-6-phosphatase (Glc6Pase), the last enzyme of gluconeogenesis, is only expressed in the liver, kidney and small intestine. The expression of the Glc6Pase gene exhibits marked specificities in the three tissues in various situations, but the molecular basis of the tissue specificity is not known. The presence of a consensus binding site of CDX proteins in the minimal Glc6Pase gene promoter has led us to consider the hypothesis that these intestine-specific CDX factors could be involved in the Glc6Pase-specific expression in the small intestine. We first show that the Glc6Pase promoter is active in both hepatic HepG2 and intestinal CaCo2 cells. Using gel shift mobility assay, mutagenesis and competition experiments, we show that both CDX1 and CDX2 can bind the minimal promoter, but only CDX1 can transactivate it. Consistently, intestinal IEC6 cells stably overexpressing CDX1 exhibit induced expression of the Glc6Pase protein. We demonstrate that a TATAAAA sequence, located in position -31/-25 relating to the transcription start site, exhibits separable functions in the preinitiation of transcription and the transactivation by CDX1. Disruption of this site dramatically suppresses both basal transcription and the CDX1 effect. The latter may be restored by inserting a couple of CDX- binding sites in opposite orientation similar to that found in the sucrase-isomaltase promoter. We also report that the specific stimulatory effect of CDX1 on the Glc6Pase TATA-box, compared to CDX2, is related to the fact that CDX1, but not CDX2, can interact with the TATA-binding protein. Together, these data strongly suggest that CDX proteins could play a crucial role in the specific expression of the Glc6Pase gene in the small intestine. They also suggest that CDX transactivation might be essential for intestine gene expression, irrespective of the presence of a functional TATA box.
Nucleic Acids Res 2003 Sep 15
PMID:Differential regulation of the glucose-6-phosphatase TATA box by intestine-specific homeodomain proteins CDX1 and CDX2. 1295 59

During infection by herpes simplex virus type 1 (HSV-1), the virion protein VP16 activates the transcription of viral immediate-early (IE) genes. Genetic and biochemical assays have shown that the potent transcriptional activation domain of VP16 can associate with general transcription factors and with chromatin-modifying coactivator proteins of several types. The latter interactions are particularly intriguing because previous reports indicate that HSV-1 DNA does not become nucleosomal during lytic infection. In the present work, chemical cross-linking and immunoprecipitation assays were used to probe the presence of activators, general transcription factors, and chromatin-modifying coactivators at IE gene promoters during infection of HeLa cells by wild-type HSV-1 and by RP5, a viral strain lacking the VP16 transcriptional activation domain. The presence of VP16 and Oct-1 at IE promoters did not depend on the activation domain. In contrast, association of RNA polymerase II, TATA-binding protein, histone acetyltransferases (p300 and CBP), and ATP-dependent remodeling proteins (BRG1 and hBRM) with IE gene promoters was observed in wild-type infections but was absent or reduced in cells infected by RP5. In contrast to the previous evidence for nonnucleosomal HSV-1 DNA, histone H3 was found associated with viral DNA at early times of infection. Interestingly, histone H3 was underrepresented on IE promoters in a manner dependent on the VP16 activation domain. Thus, the VP16 activation domain is responsible for recruiting general transcription factors and coactivators to IE promoters and also for dramatically reducing the association of histones with those promoters.
J Virol 2004 Sep
PMID:VP16-dependent association of chromatin-modifying coactivators and underrepresentation of histones at immediate-early gene promoters during herpes simplex virus infection. 1533 1

The TATA-binding protein (TBP), TFIIA, and TFIIB interact with promoter DNA to form a complex required for transcriptional initiation, and many transcriptional regulators function by either stimulating or inhibiting formation of this complex. We have recently identified TBP mutants that are viable in wild-type cells but lethal in the absence of the Nhp6 architectural transcription factor. Here we show that many of these TBP mutants were also lethal in strains with disruptions of either GCN5, encoding the histone acetyltransferase in the SAGA complex, or SWI2, encoding the catalytic subunit of the Swi/Snf chromatin remodeling complex. These synthetic lethalities could be suppressed by overexpression of TOA1 and TOA2, the genes encoding TFIIA. We also used TFIIA mutants that eliminated in vitro interactions with TBP. These viable TFIIA mutants were lethal in strains lacking Gcn5, Swi2, or Nhp6. These lethalities could be suppressed by overexpression of TBP or Nhp6, suggesting that these coactivators stimulate formation of the TBP-TFIIA-DNA complex. In vitro studies have previously shown that TBP binds very poorly to a TATA sequence within a nucleosome but that Swi/Snf stimulates binding of TBP and TFIIA. In vitro binding experiments presented here show that histone acetylation facilitates TBP binding to a nucleosomal binding site and that Nhp6 stimulates formation of a TBP-TFIIA-DNA complex. Consistent with the idea that Nhp6, Gcn5, and Swi/Snf have overlapping functions in vivo, nhp6a nhp6b gcn5 mutants had a severe growth defect, and mutations in both nhp6a nhp6b swi2 and gcn5 swi2 strains were lethal.
Mol Cell Biol 2004 Sep
PMID:Role for Nhp6, Gcn5, and the Swi/Snf complex in stimulating formation of the TATA-binding protein-TFIIA-DNA complex. 1534 90

The general transcription factor TATA-binding protein (TBP) is a key initiation factor involved in transcription by all three eukaryotic RNA polymerases. In addition, the related metazoan-specific TBP-like factor (TLF/TRF2) is essential for transcription of a distinct subset of genes. Here we characterize the vertebrate-specific TBP-like factor TBP2, using in vitro assays, in vivo antisense knockdown, and mRNA rescue experiments, as well as chromatin immunoprecipitation. We show that TBP2 is recruited to promoters in Xenopus oocytes in the absence of detectable TBP recruitment. Furthermore, TBP2 is essential for gastrulation and for the transcription of a subset of genes during Xenopus embryogenesis. In embryos, TBP2 protein is much less abundant than TBP, and moderate overexpression of TBP2 partially rescues an antisense knockdown of TBP levels and restores transcription of many TBP-dependent genes. TBP2 may be a TBP replacement factor in oocytes, whereas in embryos both TBP and TBP2 are required even though they exhibit partial redundancy and gene selectivity.
Proc Natl Acad Sci U S A 2004 Sep 14
PMID:Specialized and redundant roles of TBP and a vertebrate-specific TBP paralog in embryonic gene regulation in Xenopus. 1534 43

Plant heat shock transcription factors (HSFs) are capable of transcriptional activation (class A HSFs) or both, activation and repression (class B HSFs). However, the details of mechanism still remain unclear. It is likely, that the regulation occurs through interactions of HSFs with general transcription factors (GTFs), as has been described for numerous other transcription factors. Here, we show that class A HSFs may activate transcription through direct contacts with TATA-binding protein (TBP). Class A HSFs can also interact weakly with TFIIB. Conversely, class B HSFs inhibit promoter activity through an active mechanism of repression that involves the C-terminal regulatory region (CTR) of class B HSFs. Deletion analysis revealed two sites in the CTR of soybean GmHSFB1 potentially involved in protein-protein interactions with GTFs: one is the repressor domain (RD) located in the N-terminal half of the CTR, and the other is a TFIIB binding domain (BD) that shows affinity for TFIIB and is located C-terminally from the RD. A Gal4 DNA binding domain-RD fusion repressed activity of LexA-activators, while Gal4-BD proteins synergistically activated strong and weak transcriptional activators. In vitro binding studies were consistent with this pattern of activity since the BD region alone interacted strongly with TFIIB, and the presence of RD had an inhibitory effect on TFIIB binding and transcriptional activation.
Plant Mol Biol 2004 Sep
PMID:Plant class B HSFs inhibit transcription and exhibit affinity for TFIIB and TBP. 1560 28

In this study, we characterize the evolutionarily conserved TOUGH (TGH) protein as a novel regulator required for Arabidopsis thaliana development. We initially identified TGH as a yeast two-hybrid system interactor of the transcription initiation factor TATA-box binding protein 2. TGH has apparent orthologs in all eukaryotic model organisms with the exception of the budding yeast Saccharomyces cerevisiae. TGH contains domains with strong similarity to G-patch and SWAP domains, protein domains that are characteristic of RNA binding and processing proteins. Furthermore, TGH colocalizes with the splicing regulator SRp34 to subnuclear particles. We therefore propose that TGH plays a role in RNA binding or processing. Arabidopsis tgh mutants display developmental defects, including reduced plant height, polycotyly, and reduced vascularization. We found TGH expression to be increased in the amp1-1 mutant, which is similar to tgh mutants with respect to polycotyly and defects in vascular development. Interestingly, we observed a strong genetic interaction between TGH and AMP1 in that tgh-1 amp1-1 double mutants are extremely dwarfed and severely affected in plant development in general and vascular development in particular when compared with the single mutants.
Plant Cell 2005 Sep
PMID:The evolutionarily conserved TOUGH protein is required for proper development of Arabidopsis thaliana. 1602 89

Ankyrin defects are the most common cause of hereditary spherocytosis (HS). In some HS patients, mutations in the ankyrin promoter have been hypothesized to lead to decreased ankyrin mRNA synthesis. The ankyrin erythroid promoter is a member of the most common class of mammalian promoters which lack conserved TATA, initiator or other promoter cis elements and have high G+C content, functional Sp1 binding sites and multiple transcription initiation sites. We identified a novel ankyrin gene promoter mutation, a TG deletion adjacent to a transcription initiation site, in a patient with ankyrin-linked HS and analyzed its effects on ankyrin expression. In vitro, the mutant promoter directed decreased levels of gene expression, altered transcription initiation site utilization and exhibited defective binding of TATA-binding protein (TBP) and TFIID complex formation. In a transgenic mouse model, the mutant ankyrin promoter led to abnormalities in gene expression, including decreased expression of a reporter gene and altered transcription initiation site utilization. These data indicate that the mutation alters ankyrin gene transcription and contributes to the HS phenotype by decreasing ankyrin gene synthesis via disruption of TFIID complex interactions with the ankyrin core promoter. These studies support the model that in promoters that lack conserved cis elements, the TFIID complex directs preinitiation complex formation at specific sites in core promoter DNA and provide the first evidence that disruption of TBP binding and TFIID complex formation in this type of promoter leads to alterations in start site utilization, decreased gene expression and a disease phenotype in vivo.
Hum Mol Genet 2005 Sep 01
PMID:A dinucleotide deletion in the ankyrin promoter alters gene expression, transcription initiation and TFIID complex formation in hereditary spherocytosis. 1603 67

Initiation of transcription mediated by RNA polymerase II requires a number of transcription factors among which TFIID is the major core promoter recognition factor. TFIID is composed of highly conserved factors which include the TATA-binding protein (TBP) and about 14 TBP-associated factors (TAFs). Recently, the complete Arabidopsis TAF family has been identified. To obtain functional information about Arabidopsis TAFs, we analyzed a T-DNA insertion mutant for AtTAF6. Segregation analysis showed that plants homozygous for the mutant allele were never found, indicating that inhibition of the AtTAF6 function is lethal. Genetic experiments also revealed that the male gametophyte was affected by the attaf6 mutation since significant reduced transmission of the mutant allele through the male gametophyte was observed. Detailed histological and morphological analysis showed that the T-DNA insertion in AtTAF6 specifically affects pollen tube growth, indicating that the transcriptional regulation of only a specific subset of genes is controlled by this basal transcription factor.
Dev Biol 2005 Sep 01
PMID:The Arabidopsis TFIID factor AtTAF6 controls pollen tube growth. 1603 40

Archaeal RNA polymerases (RNAPs) are recruited to promoters through the joint action of three basal transcription factors: TATA-binding protein, TFB (archaeal homolog of TFIIB), and TFE (archaeal homolog of TFIIE). Our results demonstrate several new insights into the mechanisms of TFB and TFE during the transcription cycle. (i) The N-terminal Zn ribbon of TFB displays a surprising degree of redundancy for the recruitment of RNAP during transcription initiation in the archaeal system. (ii) The B-finger domain of TFB participates in transcription initiation events by stimulating abortive and productive transcription in a recruitment-independent function. TFB thus combines physical recruitment of the RNAP with an active role in influencing the catalytic properties of RNAP during transcription initiation. (iii) TFB mutations are complemented by TFE, thereby demonstrating that both factors act synergistically during transcription initiation. (iv) An additional function of TFE is to dynamically alter the nucleic acid-binding properties of RNAP by stabilizing the initiation complex and destabilizing elongation complexes.
Mol Cell Biol 2005 Sep
PMID:Direct modulation of RNA polymerase core functions by basal transcription factors. 1613 21


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