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

We have previously shown that transcription of the Xenopus U6 snRNA gene by RNA polymerase III is stimulated in injected Xenopus oocytes by an activator element termed the DSE, which contains an octamer sequence. Data presented here reveal that the DSE contains, in addition, a GC-rich sequence capable of binding Sp1. Both elements are required to obtain wild-type levels of U6 transcription in vivo. The Xenopus U6 DSE exhibits optimal activation properties only when positioned at its normal location upstream from the start site. The U6 Sp1 motif binds the mammalian Sp1 transcriptional activator independently of the Oct-1 protein in vitro. Those mutations that lead to a reduced transcription level in vivo abolish the binding of Sp1 in vitro. Thus, transcriptional stimulation through the Xenopus U6 Sp1 motif is likely to be mediated by a protein with DNA-binding specificity identical to mammalian Sp1. These findings support the notion that RNA polymerase II and III transcription complexes share transactivators.
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PMID:A factor with Sp1 DNA-binding specificity stimulates Xenopus U6 snRNA in vivo transcription by RNA polymerase III. 145 50

Human papillomavirus type 18 (HPV-18) infects genital squamous epithelium and is an etiological agent of cervical cancer. Cell-type-specific expression of HPV-18 is directed by the region upstream of the viral early genes that contains a transcriptional enhancer whose function is dependent solely on cellular factors. This element directs expression to high levels in squamous epithelial cells but is only weakly active in other cell types. We demonstrate by gel mobility-shift, methylation interference, and mutational analysis that the binding of two distinct factors to the enhancer is necessary for cell-type-specific transcriptional activation. One of these factors is identified as a keratinocyte-specific transcriptional activator, which we call KRF-1, while the other is a member of the AP-1 family. We also find that Oct-1 competes with KRF-1 for binding to enhancer sequences though it does not contribute to transcriptional activation. These results suggest a complex interplay of ubiquitous and cell-type-restricted transcriptional factors in the tissue- and differentiation-specific expression of HPV-18.
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PMID:A keratinocyte-specific transcription factor, KRF-1, interacts with AP-1 to activate expression of human papillomavirus type 18 in squamous epithelial cells. 165 60

The promoter specificity of transcriptional activators is generally thought to be conferred by the specificity of the DNA-binding domain, which brings the activation domain to the appropriate promoter sequence. We show here, however, that Oct-1 and Oct-2 can differentially activate transcription not through DNA binding specificity but instead through the use of promoter-selective activation domains. These distinct activation domains lead to stimulation of the U2 small nuclear RNA promoter by Oct-1 and an mRNA promoter by Oct-2. An Oct-2 variant, called Oct-2B, differs from Oct-2 by an Oct-1-related C-terminal extension that results from alternative splicing. This variant gains the ability to activate the U2 small nuclear RNA promoter. Thus, the promoter selectivity of a transcriptional activator can be changed, in this case by alternative splicing, without affecting its DNA binding specificity.
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PMID:Promoter-selective activation domains in Oct-1 and Oct-2 direct differential activation of an snRNA and mRNA promoter. 173 80

The herpes simplex virus transactivator VP16 directs the assembly of a multicomponent protein-DNA complex with cellular components Oct-1 and VCAF-1, contributing a potent carboxyl-terminal acidic activation domain that is essential for activation of gene expression in mammalian cells. We show here that VP16, devoid of this acidic activation domain, functions as a strong transcriptional activator in the yeast Saccharomyces cerevisiae when appended onto a heterologous GAL4 DNA binding domain, as determined by measuring activation of a resident GAL1:lacZ reporter gene. Deletion analysis indicated that sequences contained within the amino-terminal 369 amino acids of VP16 were necessary for transactivation by truncated VP16. Activation by truncated VP16 in yeast was comparable to that observed with a hybrid protein consisting of the GAL4 DNA binding domain linked to the VP16 acidic activation domain. Similar GAL4-VP16 hybrid proteins were only marginally active in mammalian cells. Sequence requirements for transactivation by truncated VP16 can be demarcated from domains of VP16 that are required for interaction with VCAF-1 and for protein-DNA complex formation with Oct-1. Our findings indicate that VP16 contains additional sequences upstream of the acidic activation domain that may play a direct role in transactivation.
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PMID:Transcriptional activation by DNA-binding derivatives of HSV-1 VP16 that lack the carboxyl-terminal acidic activation domain. 774 69

VP16 is a herpes simplex virus (HSV)-encoded transcriptional activator protein that is essential for efficient viral replication and as such may be a target for novel therapeutic agents directed against viral gene expression. We have reconstituted transcriptional activation by VP16 in an in vitro system that is dependent on DNA sequences from HSV immediate-early gene promoters and on protein-protein interactions between VP16 and Oct-1 that are required for VP16 activation in vivo. Activation increased synergistically with the number of TAATGARAT elements (the cis-acting element for VP16 activation in vivo) upstream of the core promoter, and mutations of this element that reduce Oct-1 or VP16 DNA binding reduced transactivation in vitro. A VP16 insertion mutant unable to interact with Oct-1 was inactive, but, surprisingly, a deletion mutant lacking the activation domain was approximately 65% as active as the full-length protein. The activation domains of Oct-1 were necessary for activation in reactions containing the VP16 deletion mutant, and they contributed significantly to activation by full-length VP16. Addition of a GA-rich element present in many HSV immediate-early gene enhancers synergistically stimulated VP16-activated transcription. Finally, oligopeptides that are derived from a region of VP16 thought to contact a cellular factor known as HCF (host cell factor) and that inhibit efficient VP16 binding to the TAATGARAT element also specifically inhibited VP16-activated, but not basal, transcription. Amino acid substitutions in one of these peptides identified three residues that are absolutely required for inhibition and presumably for interaction of VP16 with HCF.
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PMID:Transcriptional activation by herpes simplex virus type 1 VP16 in vitro and its inhibition by oligopeptides. 816 93

The herpes simplex virus VP16 protein functions as a potent transcriptional activator and targets DNA sites with the consensus TAATGARAT present in all the viral immediate-early gene promoters. To do so, VP16 directs assembly of a multiprotein complex involving two cellular proteins, host cell factor (HCF) and the Oct-1 DNA-binding transcription factor. To investigate the importance of specific protein-protein interactions to formation of this VP16-induced complex (VIC), we used oligopeptides to prevent VIC assembly. Linear and cyclic peptides corresponding to a region of VP16 previously implicated in complex formation were potent inhibitors of VIC assembly. To further characterize the protein interactions involved, we cloned a human cDNA encoding the minimal VP16 interaction domain of HCF, containing amino acids 1 to 380 [HCF (1-380)]. The REHAYS-based peptides active in preventing VIC assembly were found to specifically block binding of VP16 to HCF (1-380), without affecting VP16-Oct-1 binding. The inhibitory activity of these VP16 peptides was strictly sequence specific for the EHAY residues. Site-directed mutagenesis of the HCF (1-380) domain revealed residues E102 and K105 to be critical determinants in support of VIC formation. Alteration of a single residue in HCF, K105, was shown to virtually abolish complex assembly. Interestingly however, none of the HCF mutants that were impaired in their ability to support complex formation exhibited defects in direct VP16 binding, supporting loss of function at a higher order in complex assembly.
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PMID:Protein interactions in the herpes simplex virus type 1 VP16-induced complex: VP16 peptide inhibition and mutational analysis of host cell factor requirements. 909 65

Tissue-restricted POU domain transcription factors, which bind octamer or octamer-like gene sequences, play roles in cellular differentiation and the development of several organs. We have previously identified a POU domain gene, Skn-1a/i, expressed primarily in epidermis, that encodes at least two products through alternative splicing. One of these, Skn-1a, acts as a transcriptional activator, and the other, Skn-1i, contains an inhibitory domain in the NH2 terminus, which prevents DNA-binding in vitro and transcriptional activation in vivo. We now demonstrate that when Skn-1i is expressed in eukaryotic cells it can bind to an octamer site, suggesting that in vivo cellular factors modulate the activity of the inhibitory domain to permit DNA-binding. Yet the inhibitory domain does not allow transactivation by Skn-1i or by a heterologous transactivator containing this domain in cis. Furthermore, we demonstrate that Skn-1a, Tst-1, and Oct-1 are the major octamer-binding proteins in epidermis. Since Skn-1a is primarily expressed in suprabasal cells of the epidermis, we have tested its possible role in the regulation of epidermal papillomaviruses. In transient transfection assays, Skn-1a and Tst-1 can activate the long control region of the epidermis-specific human papillomavirus 1A (HPV-1A). Consistent with these in vivo transcription data, in vitro DNA binding studies identify three octamer-like sites, which are capable of binding Skn-1a, in the HPV-1A long control region. Mutations of all three octamer-like sites prevent transactivation by Skn-1a in transient transfection assays. Taken together, these results provide evidence that Skn-1a and Tst-1 may provide a molecular link between HPV gene expression and epidermal differentiation.
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PMID:Characterization of Skn-1a/i POU domain factors and linkage to papillomavirus gene expression. 918 90

Interleukin-5 (IL-5) controls the development of eosinophilia and contributes to a number of disease states including asthma. Expression of IL-5 is inducible under tight transcriptional regulation. This requires the contribution of several promoter elements; however, the conserved lymphokine element 0 (CLE0) in particular, is essential for expression of IL-5. In this study, we report the nuclear factors which regulate human IL-5 CLE0 activity in the human cell line PER-117. Using specific antibodies, we identified the transcriptional factors Oct-1 and Oct-2 binding to the 5' region of the CLE0 element. The involvement of Oct factors with CLE0 has not been reported previously in any of the lymphokines. In addition, the CLE0 element also appeared to complex with the transcriptional activator AP-1, consisting of the family members Jun D and Fra-2. We observed the binding of Oct-1 to be constitutive in comparison to Oct-2 and AP-1, both of which were induced in response to cell activation by PMA/A23187. Although the interaction of all three factors with CLE0 was closely linked and overlapping, residues critical to their binding were identified. We demonstrate, using site-directed mutagenesis and cotransfection experiments, that the CLE0 element is indispensable for IL-5 promoter activity and that Octamer factors contribute to the positive regulation of the hIL-5 gene.
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PMID:The activity of the human interleukin-5 conserved lymphokine element 0 is regulated by octamer factors in human cells. 1049 Nov 86

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

Upon infection, the herpes simplex virus (HSV) transcriptional activator VP16 directs the formation of a multiprotein-DNA complex-the VP16-induced complex-with two cellular proteins, the host cell factor HCF-1 and the POU domain transcription factor Oct-1, on TAATGARAT-containing sequences found in the promoters of HSV immediate-early genes. HSV VP16 contains carboxy-terminal sequences important for transcriptional activation and a central conserved core that is important for VP16-induced complex assembly. On its own, VP16 displays little, if any, sequence-specific DNA-binding activity. We show here that, within the VP16-induced complex, however, the VP16 core has an important role in DNA binding. Mutation of basic residues on the surface of the VP16 core reveals a novel DNA-binding surface with essential residues which are conserved among VP16 orthologs. These results illuminate how, through association with DNA, VP16 is able to interpret cis-regulatory signals in the DNA to direct the assembly of a multiprotein-DNA transcriptional regulatory complex.
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PMID:DNA recognition by the herpes simplex virus transactivator VP16: a novel DNA-binding structure. 1141 46


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