Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

TFIID is a multiprotein complex consisting of the TATA box binding protein and multiple tightly associated proteins (TAFIIs) that are required for transcription by selected activators. We previously reported cloning and partial characterization of human TAFII130 (hTAFII130). The central domain of hTAFII130 contains four glutamine-rich regions, designated Q1 to Q4, that are involved in interactions with the transcriptional activator Sp1. Mutational analysis has revealed specific regions within the glutamine-rich (Q1 to Q4) central region of hTAFII130 that are required for interaction with distinct activation domains. We tested amino- and carboxyl-terminal deletions of hTAFII130 for interaction with Sp1 activation domains A and B (Sp1A and Sp1B) and the N-terminal activation domain of CREB (CREB-N) by using the yeast two-hybrid system. Our results indicate that Sp1B interacts almost exclusively with the Q1 region of hTAFII130. In contrast, Sp1A makes multiple contacts with Q1 to Q4 of hTAFII130, while CREB-N interacts primarily with the Q1-Q2 hTAFII130 subdomain. Consistent with these interaction studies, overexpression of the Q1-to-Q4 region in HeLa cells inhibits Sp1- but not VP16-mediated transcriptional activation. These findings indicate that the Q1-to-Q4 region of hTAFII130 is required for Sp1-mediated transcriptional enhancement in mammalian cells and that different activation domains target distinct subdomains of hTAFII130.
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PMID:Distinct subdomains of human TAFII130 are required for interactions with glutamine-rich transcriptional activators. 974 90

The yeast transcriptional activator ADR1, which is required for ADH2 and other genes' expression, contains four transactivation domains (TADs). While previous studies have shown that these TADs act through GCN5 and ADA2, and presumably TFIIB, other factors are likely to be involved in ADR1 function. In this study, we addressed the question of whether TFIID is also required for ADR1 action. In vitro binding studies indicated that TADI of ADR1 was able to retain TAFII90 from yeast extracts and TADII could retain TBP and TAFII130/145. TADIV, however, was capable of retaining multiple TAFIIs, suggesting that TADIV was binding TFIID from yeast whole-cell extracts. The ability of TADIV truncation derivatives to interact with TFIID correlated with their transcription activation potential in vivo. In addition, the ability of LexA-ADR1-TADIV to activate transcription in vivo was compromised by a mutation in TAFII130/145. ADR1 was found to associate in vivo with TFIID in that immunoprecipitation of either TAFII90 or TBP from yeast whole-cell extracts specifically coimmunoprecipitated ADR1. Most importantly, depletion of TAFII90 from yeast cells dramatically reduced ADH2 derepression. These results indicate that ADR1 physically associates with TFIID and that its ability to activate transcription requires an intact TFIID complex.
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PMID:ADR1-mediated transcriptional activation requires the presence of an intact TFIID complex. 974 3

The transcriptional activity of an in vitro assembled human interferon-beta gene enhanceosome is highly synergistic. This synergy requires five distinct transcriptional activator proteins (ATF2/c-JUN, interferon regulatory factor 1, and p50/p65 of NF-kappaB), the high mobility group protein HMG I(Y), and the correct alignment of protein-binding sites on the face of the DNA double helix. Here, we investigate the mechanisms of enhanceosome-dependent transcriptional synergy during preinitiation complex assembly in vitro. We show that the stereospecific assembly of the enhanceosome is critical for the efficient recruitment of TFIIB into a template-committed TFIID-TFIIA-USA (upstream stimulatory activity complex) and for the subsequent recruitment of the RNA polymerase II holoenzyme complex. In addition, we provide evidence that recruitment of the holoenzyme by the enhanceosome is due, at least in part, to interactions between the enhanceosome and the transcriptional coactivator CREB, cAMP responsive element binding protein (CBP). These studies reveal a unique role of enhanceosomes in the cooperative assembly of the transcription machinery on the human interferon-beta promoter.
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PMID:Efficient recruitment of TFIIB and CBP-RNA polymerase II holoenzyme by an interferon-beta enhanceosome in vitro. 977 Apr 62

In yeast cells, interaction between a DNA-bound protein and a single component of the RNA polymerase II (poIII) holoenzyme is sufficient to recruit the latter to a promoter and thereby activate gene transcription. Here we review results which have suggested such a simple mechanism for how genes can be turned on. The series of experiments which eventually led to this model was originally instigated by studying gene expression in a yeast strain which carries a point mutation in Gal11, a component of the poIII holoenzyme. In cells containing this mutant protein termed Gall11P, a derivative of the transcriptional activator Gal4 devoid of any classical activating region is turned into a strong activator. This activating function acquired by an otherwise silent DNA-binding protein is solely due to a novel and fortuitous interaction between Gal11P and a fragment of the Gal4 dimerization region generated by the P mutation. The simplest explanation for these results is that tethering Gal11 to DNA recruits the poIII holoenzyme and, consequently, activates gene transcription. Transcription factors that are believed not to be integral part of the poIII holoenzyme but are nevertheless required for this instance of gene activation, e.g. the TATA-binding TFIID complex, may bind DNA cooperatively with the holoenzyme when recruited to a promoter, thus forming a complete poIII preinitiation complex. One prediction of this model is that recruitment of the entire poIII transcription complex and consequent gene activation can be achieved by tethering different components to DNA. Indeed, fusion of a DNA-binding domain to a variety of poIII holoenzyme components and TFIID subunits leads to activation of genes bearing the recognition site for the DNA-binding protein. These results imply that accessory factors, which are required to remove or modify nucleosomes do not need to be directly contacted by activators, but can rather be engaged in the activation process when the poIII complex is recruited to DNA. In fact, recruitment of the poIII holoenzyme suffices to remodel nucleosomes at the PHO5 promoter and presumably at many other promoters. Other events in the process of gene expression following recruitment of the transcription complex, e.g. initiation, promoter clearance, elongation and termination, could unravel as a consequence of the recruitment step and the formation of an active preinitiation complex on DNA. This view does not exclude the possibility that classical activators also act directly on chromatin remodeling and post-recruitment steps to regulate gene expression.
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PMID:Recruitment of the RNA polymerase II holoenzyme and its implications in gene regulation. 989 6

Early embryonic development in Xenopus laevis is characterized by transcriptional repression which is relieved at the midblastula stage (MBT). Here we show that the relative abundance of TATA-binding protein (TBP) increases robustly at the MBT and that the mechanism underlying this increase is translation of maternally stored TBP RNA. We show that TBP is rate-limiting in egg extract under conditions that titrate nucleosome assembly. Precocious translation of TBP mRNA in Xenopus embryos facilitates transcription before the MBT, without requiring TBP to be prebound to the promoter before injection. This effect is transient in the absence of chromatin titration and is sustained when chromatin is titrated. These data show that translational regulation of TBP RNA contributes to limitations on the transcriptional capacity before the MBT. Second, we examined the ability of trans-acting factors to contribute to promoter activity before the MBT. Deletion of cis-acting elements does not affect histone H2B transcription in egg extract, a finding indicative of limited trans-activation. Moreover, in the context of the intact promoter, neither the transcriptional activator Oct-1, nor TBP, nor TFIID enable transcriptional activation in vitro. HeLa cell extract, however, reconstitutes activated transcription in mixed extracts. These data suggest a deficiency in egg extract cofactors required for activated transcription. We show that the capacity for activated H2B transcription is gradually acquired at the early gastrula transition. This transition occurs well after the blastula stage when the basal transcription machinery can first be complemented with TBP.
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PMID:Translation of maternal TATA-binding protein mRNA potentiates basal but not activated transcription in Xenopus embryos at the midblastula transition. 1056 23

Transcription in human papillomaviruses (HPVs) is mainly regulated by cellular transcription factors and virus-encoded E2 proteins that act as sequence-specific DNA-binding proteins. Although the functions of E2 as a transcriptional activator and a repressor have been well documented, the role of cellular factors involved in E2-mediated regulation of the HPV promoters and the mechanism by which E2 modulates viral gene expression remain unclear. Using reconstituted cell-free transcription systems, we found that cellular enhancer-binding factors and general cofactors, such as TAF(II)s, TFIIA, Mediator, and PC4, are not required for E2-mediated repression. Unlike other transcriptional repressors that function through recruitment of histone deacetylase or corepressor complexes, HPV E2 is able to directly target components of the general transcription machinery to exert its repressor activity on the natural HPV E6 promoter. Interestingly, preincubation of TATA binding protein (TBP) or TFIID with HPV template is not sufficient to overcome E2-mediated repression, which can be alleviated only via formation of a minimal TBP (or TFIID)-TFIIB-RNA polymerase II-TFIIF preinitiation complex. Our data therefore indicate that E2 does not simply work by displacing TBP or TFIID from binding to the adjacent TATA box. Instead, E2 appears to function as an active repressor that directly inhibits HPV transcription at steps after TATA recognition by TBP or TFIID.
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PMID:Alleviation of human papillomavirus E2-mediated transcriptional repression via formation of a TATA binding protein (or TFIID)-TFIIB-RNA polymerase II-TFIIF preinitiation complex. 1059 14

Human T-cell leukemia virus type 1 (HTLV-1) encodes a transcriptional activator, Tax, whose activity is believed to contribute significantly to cellular transformation. Tax stimulates transcription from the proviral promoter as well as from promoters for a variety of cellular genes. The mechanism through which Tax communicates to the general transcription factors and RNA polymerase II has not been completely determined. We investigated whether Tax could function directly through the general transcription factors and RNA polymerase II or if other intermediary factors or coactivators were required. Our results show that a system consisting of purified recombinant TFIIA, TFIIB, TFIIE, TFIIF, CREB, and Tax, along with highly purified RNA polymerase II, affinity-purified epitope-tagged TFIID, and semipurified TFIIH, supports basal transcription of the HTLV-1 promoter but is not responsive to Tax. Two additional activities were required for Tax to stimulate transcription. We demonstrate that one of these activities is poly(ADP-ribose) polymerase (PARP), a molecule that has been previously identified to be the transcriptional coactivator PC1. PARP functions as a coactivator in our assays at molar concentrations approximately equal to those of the DNA and equal to or less than those of the transcription factors in the assay. We further demonstrate that PARP stimulates Tax-activated transcription in vivo, demonstrating that this biochemical approach has functionally identified a novel target for the retroviral transcriptional activator Tax.
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PMID:Identification of poly(ADP-ribose) polymerase as a transcriptional coactivator of the human T-cell leukemia virus type 1 Tax protein. 1066 46

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

Expression of human T-cell leukemia virus type 1 (HTLV-1) is regulated by the viral transcriptional activator Tax. Tax activates viral transcription through interaction with the cellular transcription factor CREB and the coactivators CBP/p300. One key property of the coactivators is the presence of histone acetyltransferase (HAT) activity, which enables p300/CBP to modify nucleosome structure. The data presented in this manuscript demonstrate that full-length p300 and CBP facilitate transcription of a reconstituted chromatin template in the presence of Tax and CREB. The ability of p300 and CBP to activate transcription from the chromatin template is dependent upon the HAT activity. Moreover, the coactivator HAT activity must be tethered to the template by Tax and CREB, since a p300 mutant that fails to interact with Tax did not facilitate transcription or acetylate histones. p300 acetylates histones H3 and H4 within nucleosomes located in the promoter and 5' proximal regions of the template. Nucleosome acetylation is accompanied by an increase in the level of binding of RNA polymerase II transcription factor TFIID and RNA polymerase II to the promoter. Interestingly, we found distinct transcriptional activities between CBP and p300. CBP, but not p300, possesses an N-terminal activation domain which directly activates Tax-mediated HTLV-1 transcription from a naked DNA template. Finally, using the chromatin immunoprecipitation assay, we provide the first direct experimental evidence that p300 and CBP are associated with the HTLV-1 long terminal repeat in vivo.
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PMID:Acetylation of nucleosomal histones by p300 facilitates transcription from tax-responsive human T-cell leukemia virus type 1 chromatin template. 1205 56

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


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