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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chromatin structure of the Saccharomyces cerevisiae ADH2 gene is modified during the switch from repressing (high glucose) to derepressing (low glucose) conditions of growth. Loss of protection toward micrococcal nuclease cleavage for the nucleosomes covering the TATA box and the RNA initiation sites (-1 and +1, respectively) is the major modification taking place and is strictly dependent on the presence of the transcriptional activator ADR1. To identify separate functions involved in the transition from a repressed to a transcribing promoter, we have analyzed the ADH2 chromatin organization in various genetic backgrounds. Deletion of the CCR4 gene coding for a general transcription factor impaired ADH2 expression without affecting chromatin remodeling. Growing yeast at 37 degrees C also resulted in chromatin remodeling at the ADH2 locus even under glucose repressing conditions. However, although this temperature-induced remodeling was dependent on the ADR1 protein, no ADH2 mRNA was observed. In addition, inactivating RNA polymerase II (and therefore, elongation) was found to have no effect on the ability to reconfigure nucleosomes. Taken together, these data indicate that chromatin remodeling by itself is insufficient to induce transcription at the ADH2 promoter.
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PMID:Factors affecting Saccharomyces cerevisiae ADH2 chromatin remodeling and transcription. 938 26

Drosophila heat shock factor (HSF) binds to specific sequence elements of heat shock genes and can activate their transcription 200-fold. Though HSF has an acidic activation domain, the mechanistic details of heat shock gene activation remain undefined. Here we report that HSF interacts directly with the general transcription factor TBP (TATA-box binding protein), and these two factors bind cooperatively to heat shock promoters. A third factor that binds heat shock promoters, GAGA factor, also interacts with HSF and further stabilizes HSF binding to heat shock elements (HSEs). The interaction of HSF and TBP is explored in some detail here and is shown to be mediated by residues in both the amino- and carboxyl-terminal portions of HSF. This HSF/TBP interaction can be specifically disrupted by competition with the potent acidic transcriptional activator VP16. We further show that the acidic domain of the largest subunit of Drosophila RNA polymerase II (Pol II) associates with TBP in vitro and is specifically displaced from TBP upon addition of HSF. The region of TBP that mediates both HSF and Pol II acidic domain binding maps to the conserved carboxyl-terminal repeats and depends on at least one of the TBP residues known to be contacted by VP16 and to be critical for transcription activation. We discuss these findings in the context of a model in which HSF triggers hsp70 transcription by freeing the hsp70 promoter-paused Pol II from the constraints on elongation caused by the affinity of Pol II for general transcription factors.
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PMID:Cooperative and competitive protein interactions at the hsp70 promoter. 940 12

Multiprotein bridging factor 1 (MBF1) is a coactivator which mediates transcriptional activation by interconnecting the general transcription factor TATA element-binding protein and gene-specific activators such as the Drosophila nuclear receptor FTZ-F1 or the yeast basic leucine zipper protein GCN4. The human homolog of MBF1 (hMBF1) has been identified but its function, especially in transcription, remains unclear. Here we report the cDNA cloning and functional analysis of hMBF1. Two isoforms, which we term hMBF1alpha and hMBF1beta, have been identified. hMBF1alpha mRNA was detected in a number of tissues, whereas hMBF1beta exhibited tissue-specific expression. Both isoforms bound to TBP and Ad4BP/SF-1, a mammalian counterpart of FTZ-F1, and mediated Ad4BP/SF-1-dependent transcriptional activation. While hMBF1 was detected in the cytoplasm by immunostaining, coexpression of the nuclear protein Ad4BP/SF-1 with hMBF1 induced accumulation of hMBF1 in the nucleus, suggesting that hMBF1 is localized in the nucleus through its binding to Ad4BP/SF-1. hMBF1 also bound to ATF1, a member of the basic leucine zipper protein family, and mediated its activity as a transcriptional activator. These data establish that the coactivator MBF1 is functionally conserved in eukaryotes.
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PMID:The role of human MBF1 as a transcriptional coactivator. 1056 91

The general transcription factor TFIIB plays a crucial role in the assembly of the transcriptional preinitiation complex and has also been proposed as a target of transcriptional activator proteins (reviewed in [1]). TFIIB is composed of two domains which are engaged in an intramolecular interaction that is disrupted upon interaction with the activation domain of the Herpesvirus VP16 protein in vitro [2] [3]. The significance of this event for transcriptional activation is not known, however. The amino-terminal intramolecular interaction domain is the most conserved region of TFIIB and plays a role in transcription start-site selection [4] [5] [6]. In addition, we have shown previously that the integrity of this region is required for transcriptional activation in vivo [4]. Here, we have defined a charge cluster at the amino terminus of TFIIB that is required for transcriptional activation in vivo. We found that this domain determines the affinity of the TFIIB intramolecular interaction and the ability of TFIIB to interact with a transcriptional activation domain, but not with components of the holoenzyme. Our results suggest that the intramolecular interaction in TFIIB regulates transcriptional activation in vivo.
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PMID:The conformation of the transcription factor TFIIB modulates the response to transcriptional activators in vivo. 1071 6

Human MDM2 (hMDM2) inhibits transcriptional activation mediated by wild-type p53 and its tumor-derived mutants. We present evidence to show that hMDM2 interacts with the tumor-derived mutants of p53 and inhibits transcriptional activation of the human c-myc promoter mediated by the tumor-derived mutants of p53 through two domains. These two domains of hMDM2 are able to function independent of each other. Interaction with either of the domains is sufficient for inhibition of mutant p53-mediated transactivation. One of these domains is the same as the wild-type p53 interaction domain of hMDM2, whereas a second domain is situated within amino acid 190 and 276 residues and is specific for mutant p53. hMDM2 does not inhibit transcriptional activation mediated by the transcriptional activator VP16, suggesting that the inhibition is not mediated by inactivation of a general transcription factor. The transactivation and the oligomerization domains of mutant p53 are dispensable for its interaction with hMDM2. Thus, both hMDM2 and p53 recognize each other through unique domains. These observations suggest that forms of hMDM2 incapable of interacting with the wild-type p53, and are often expressed in transformed cells, would inhibit mutant p53-mediated transactivation and antagonize the tumorigenic function of mutant p53. This inhibitory function of hMDM2 may account for infrequent co-occurrence of p53 mutation and hMDM2 overexpression in cancer cells. Our results also suggest distinct mechanisms for wild-type and mutant p53-mediated transcriptional activation.
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PMID:The human oncoprotein MDM2 uses distinct strategies to inhibit transcriptional activation mediated by the wild-type p53 and its tumor-derived mutants. 1117 71

Human TAF(II)55 (hTAF(II)55) is a component of the multisubunit general transcription factor TFIID and has been shown to mediate the functions of many transcriptional activators via direct protein-protein interactions. To uncover the regulatory properties of the general transcription machinery, we have isolated the hTAF(II)55 gene and dissected the regulatory elements and the core promoter responsible for hTAF(II)55 gene expression. Surprisingly, the hTAF(II)55 gene has a single uninterrupted open reading frame and is the only intronless general transcription factor identified so far. Its expression is driven by a TATA-less promoter that contains a functional initiator and a downstream promoter element, as illustrated by both transfection assays and mutational analyses. Moreover, this core promoter can mediate the activity of a transcriptional activator that is artificially recruited to the promoter in a heterologous context. Interestingly, in the promoter-proximal region there are multiple Sp1-binding sites juxtaposed to a single AP2-binding site, indicating that Sp1 and AP2 may regulate the core promoter activity of the hTAF(II)55 gene. These findings indicate that a combinatorial regulation of a general transcription factor-encoding gene can be conferred by both ubiquitous and cell type-specific transcriptional regulators.
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PMID:The intronless and TATA-less human TAF(II)55 gene contains a functional initiator and a downstream promoter element. 1134 78

We report that RapA, an Escherichia coli RNA polymerase (RNAP)-associated homolog of SWI2/SNF2, is capable of dramatic activation of RNA synthesis. The RapA-mediated transcriptional activation in vitro depends on supercoiled DNA and high salt concentrations, a condition that is likely to render the DNA superhelix tightly compacted. Moreover, RapA activates transcription by stimulating RNAP recycling. Mutational analyses indicate that the ATPase activity of RapA is essential for its function as a transcriptional activator, and a rapA null mutant exhibits a growth defect on nutrient plates containing high salt concentrations in vivo. Thus, RapA acts as a general transcription factor and an integral component of the transcription machinery. The mode of action of RapA in remodeling posttranscription or posttermination complexes is discussed.
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PMID:RapA, a bacterial homolog of SWI2/SNF2, stimulates RNA polymerase recycling in transcription. 1175 38

The core components of the archaeal transcription apparatus closely resemble those of eukaryotic RNA polymerase II, while the DNA-binding transcriptional regulators are predominantly of bacterial type. Here we report the construction of an entirely recombinant system for positively regulated archaeal transcription. By omitting individual subunits, or sets of subunits, from the in vitro assembly of the 12-subunit RNA polymerase from the hyperthermophile Methanocaldococcus jannaschii, we describe a functional dissection of this RNA polymerase II-like enzyme, and its interactions with the general transcription factor TFE, as well as with the transcriptional activator Ptr2.
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PMID:A fully recombinant system for activator-dependent archaeal transcription. 1548 36

Accurate transcription of a gene by RNA polymerase II requires the assembly of a group of general transcription factors at the promoter. The general transcription factor TFIIB plays a central role in preinitiation complex assembly, providing a bridge between promoter-bound TFIID and RNA polymerase II. TFIIB makes extensive contact with the core promoter via two independent DNA-recognition modules. In addition to interacting with other general transcription factors, TFIIB directly modulates the catalytic center of RNA polymerase II in the transcription complex. Moreover, TFIIB has been proposed as a target of transcriptional activator proteins that act to stimulate preinitiation complex assembly. In this review, we will discuss our current understanding of these activities of TFIIB.
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PMID:TFIIB and the regulation of transcription by RNA polymerase II. 1759 82

Transcription of eukaryotic messenger RNA (mRNA) encoding genes by RNA polymerase II (Pol II) is triggered by the binding of transactivating proteins to enhancer DNA, which stimulates the recruitment of general transcription factors (TFIIA, B, D, E, F, H) and Pol II on the cis-linked promoter, leading to pre-initiation complex formation and transcription. In TFIID-dependent activation pathways, this general transcription factor containing TATA-box-binding protein is first recruited on the promoter through interaction with activators and cooperates with TFIIA to form a committed pre-initiation complex. However, neither the mechanisms by which activation signals are communicated between these factors nor the structural organization of the activated pre-initiation complex are known. Here we used cryo-electron microscopy to determine the architecture of nucleoprotein complexes composed of TFIID, TFIIA, the transcriptional activator Rap1 and yeast enhancer-promoter DNA. These structures revealed the mode of binding of Rap1 and TFIIA to TFIID, as well as a reorganization of TFIIA induced by its interaction with Rap1. We propose that this change in position increases the exposure of TATA-box-binding protein within TFIID, consequently enhancing its ability to interact with the promoter. A large Rap1-dependent DNA loop forms between the activator-binding site and the proximal promoter region. This loop is topologically locked by a TFIIA-Rap1 protein bridge that folds over the DNA. These results highlight the role of TFIIA in transcriptional activation, define a molecular mechanism for enhancer-promoter communication and provide structural insights into the pathways of intramolecular communication that convey transcription activation signals through the TFIID complex.
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PMID:TFIIA and the transactivator Rap1 cooperate to commit TFIID for transcription initiation. 2055 89


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