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

The yeast CUP1 gene is activated by the copper-dependent binding of the transcriptional activator, Ace1p. An episome containing transcriptionally active or inactive CUP1 was purified in its native chromatin structure from yeast cells. The amount of RNA polymerase II on CUP1 in the purified episomes correlated with its transcriptional activity in vivo. Chromatin structures were examined by using the monomer extension technique to map translational positions of nucleosomes. The chromatin structure of an episome containing inactive CUP1 isolated from ace1Delta cells is organized into clusters of overlapping nucleosome positions separated by linkers. Novel nucleosome positions that include the linkers are occupied in the presence of Ace1p. Repositioning was observed over the entire CUP1 gene and its flanking regions, possibly over the entire episome. Mutation of the TATA boxes to prevent transcription did not prevent repositioning, implicating a chromatin remodeling activity recruited by Ace1p. These observations provide direct evidence in vivo for the nucleosome sliding mechanism proposed for remodeling complexes in vitro and indicate that remodeling is not restricted to the promoter but occurs over a chromatin domain including CUP1 and its flanking sequences.
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PMID:Remodeling of yeast CUP1 chromatin involves activator-dependent repositioning of nucleosomes over the entire gene and flanking sequences. 1113 41

Transcriptional regulation is all about getting RNA polymerase to the right place on the gene at the right time and making sure that it is competent to conduct transcription. Traditional views of this process place most of their emphasis on the events that precede initiation of transcription. We imagine a promoter-bound transcriptional activator (or collection of activators) recruiting components of the basal transcriptional machinery to the DNA, eventually leading to the recruitment of RNA polymerase II and the onset of gene transcription. Although these events play a crucial role in regulating gene expression, they are only half the story. Correct regulation of transcription requires that polymerase not only initiates when and where it should, but that it stops initiating when no longer appropriate. But how are the signals from transcriptional activators, telling RNA polymerase to fire, terminated? Is this process governed by chance, with activators simply falling off the promoter at a certain frequency? Or is there some more direct mechanism, whereby activators are aggressively limited from uncontrolled promoter activation? A new article by suggests the latter may be true, and provides a mechanism for how a component of the basal transcription machinery can mark the activators it has encountered, sentencing them to an early death or banishing them from the nucleus. The ability of the basal transcriptional apparatus to mark activators provides an efficient way to limit activator function and ensures that continuing transcription initiation at a promoter is coupled to the continuing synthesis and activation of transcriptional activators.
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PMID:Transcriptional activation: risky business. 1133 4

The budding yeast transcriptional activator Gcn4 is rapidly degraded in an SCF(Cdc4)-dependent manner in vivo. Upon fractionation of yeast extracts to identify factors that mediate Gcn4 ubiquitination, we found that Srb10 phosphorylates Gcn4 and thereby marks it for recognition by SCF(Cdc4) ubiquitin ligase. Srb10 is a physiological regulator of Gcn4 stability because both phosphorylation and turnover of Gcn4 are diminished in srb10 mutants. Gcn4 is almost completely stabilized in srb10Delta pho85Delta cells, or upon mutation of all Srb10 phosphorylation sites within Gcn4, suggesting that the Pho85 and Srb10 cyclin-dependent kinases (CDKs) conspire to limit the accumulation of Gcn4. The multistress response transcriptional regulator Msn2 is also a substrate for Srb10 and is hyperphosphorylated in an Srb10-dependent manner upon heat-stress-induced translocation into the nucleus. Whereas Msn2 is cytoplasmic in resting wild-type cells, its nuclear exclusion is partially compromised in srb10 mutant cells. Srb10 has been shown to repress a subset of genes in vivo, and has been proposed to inhibit transcription via phosphorylation of the C-terminal domain of RNA polymerase II. We propose that Srb10 also inhibits gene expression by promoting the rapid degradation or nuclear export of specific transcription factors. Simultaneous down-regulation of both transcriptional regulatory proteins and RNA polymerase may enhance the potency and specificity of transcriptional inhibition by Srb10.
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PMID:Negative regulation of Gcn4 and Msn2 transcription factors by Srb10 cyclin-dependent kinase. 1133 99

The nature of the interaction of coactivator proteins with transcriptionally active promoters in chromatin is a fundamental question in transcriptional regulation by RNA polymerase II. In this study, we used a biochemical approach to examine the functional association of the coactivator p300 with chromatin templates. Using in vitro transcription template competition assays, we observed that p300 forms a stable, template-committed complex with chromatin during the transcription process. The template commitment is dependent on the time of incubation of p300 with the chromatin template and occurs independently of the presence of a transcriptional activator protein. In studies examining interactions between p300 and chromatin, we found that p300 binds directly to chromatin and that the binding requires the p300 bromodomain, a conserved 110-amino-acid sequence found in many chromatin-associated proteins. Furthermore, we observed that the isolated p300 bromodomain binds directly to histones, preferentially to histone H3. However, the isolated p300 bromodomain does not bind to nucleosomal histones under the same assay conditions, suggesting that free histones and nucleosomal histones are not equivalent as binding substrates. Collectively, our results suggest that the stable association of p300 with chromatin is mediated, at least in part, by the bromodomain and is critically important for p300 function. Furthermore, our results suggest a model for p300 function that involves distinct activator-dependent targeting and activator-independent chromatin binding activities.
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PMID:p300 forms a stable, template-committed complex with chromatin: role for the bromodomain. 1135 96

The posttranslational modification of eukaryotic intracellular proteins by O-linked N-acetylglucosamine (O-GlcNAc) monosaccharides is essential for cell viability, yet its precise functional roles are largely unknown. O-GlcNAc transferase utilizes UDP-GlcNAc, the end product of hexosamine biosynthesis, to catalyze this modification. The availability of UDP-GlcNAc correlates with glycosylation levels of intracellular proteins as well as with transcriptional levels of some genes. Meanwhile, transcription factors and RNA polymerase II can be modified by O-GlcNAc. A linkage between transcription factor O-GlcNAcylation and transcriptional regulation therefore has been postulated. Here, we show that O-GlcNAcylation of a chimeric transcriptional activator containing the second activation domain of Sp1 decreases its transcriptional activity both in an in vitro transcription system and in living cells, which is in concert with our observation that O-GlcNAcylation of Sp1 activation domain blocks its in vitro and in vivo interactions with other Sp1 molecules and TATA-binding protein-associated factor II 110. Furthermore, overexpression of O-GlcNAc transferase specifically inhibits transcriptional activation by native Sp1 in cells. Thus, our studies provide direct evidence that O-GlcNAcylation of transcription factors is involved in transcriptional regulation.
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PMID:O-linkage of N-acetylglucosamine to Sp1 activation domain inhibits its transcriptional capability. 1137 15

Sip4 is a Zn(2)Cys(6) transcriptional activator that binds to the carbon source-responsive elements of gluconeogenic genes in Saccharomyces cerevisiae. The Snf1 protein kinase interacts with Sip4 and regulates its phosphorylation and activator function in response to glucose limitation; however, evidence suggested that another kinase also regulates Sip4. Here we examine the role of the Srb10 kinase, a component of the RNA polymerase II holoenzyme that has been primarily implicated in transcriptional repression but also positively regulates Gal4. We show that Srb10 is required for phosphorylation of Sip4 during growth in nonfermentable carbon sources and that the catalytic activity of Srb10 stimulates the ability of LexA-Sip4 to activate transcription of a reporter. Srb10 and Sip4 coimmunoprecipitate from cell extracts and interact in two-hybrid assays, suggesting that Srb10 regulates Sip4 directly. We also present evidence that the Srb10 and Snf1 kinases interact with different regions of Sip4. These findings support the view that the Srb10 kinase not only plays negative roles in transcriptional control but also has broad positive roles during growth in carbon sources other than glucose.
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PMID:Interaction of the Srb10 kinase with Sip4, a transcriptional activator of gluconeogenic genes in Saccharomyces cerevisiae. 1148 18

The involvement of chromatin structure and organization in transcriptional regulatory pathways has become evident. One unsolved question concerns the molecular mechanisms of chromatin remodeling during in vivo promoter activation. By using a high resolution in vivo analysis we show that when yeast cells are exposed to a regulatory signal the positions of specific nucleosomes change. The system analyzed consists of the basic elements of the Saccharomyces cerevisiae ADH2 promoter, two nucleosomes of which are shown to change the distribution of their positions by few nucleotides in the direction of transcription when the glucose content of the medium is lowered. Such repositioning does not occur in the absence of the ADH2 transcriptional activator Adr1 or in the presence of its DNA-binding domain alone. A construct consisting of the DNA-binding domain plus a 43-amino acid peptide containing the Adr1 activation domain is sufficient to induce the same effect of the full-length protein. Nucleosome repositioning occurs even when the catalytic activity of the RNA polymerase II is impaired, suggesting that the Adr1 activation domain mediates the recruitment of some factor to correctly preset the relevant sequences for the subsequent transcription steps.
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PMID:In vivo changes of nucleosome positioning in the pretranscription state. 1174 18

Hepatitis B virus (HBV) gene expression is mainly regulated at the transcription initiation level. The viral X protein (pX) is a transcription coactivator/mediator targeting TFIIB for the recruitment of RNA polymerase II. Here we report a novel pX nuclear target designated HBXAP (hepatitis B virus X-associated protein). HBXAP is a novel cellular nuclear protein containing a PHD (plant homology domain) finger, a domain shared by many proteins that play roles in chromatin remodeling, transcription coactivation, and oncogenesis. pX physically interacts with HBXAP in vitro and in vivo via the HBXAP region containing the PHD finger. At the functional level HBXAP increases HBV transcription in a pX-dependent manner suggesting a role for this interaction in the virus life cycle. Interestingly, HBXAP collaborates with pX in coactivating the transcriptional activator NF-kappaB. Coactivation of NF-kappaB was also observed in tumor necrosis factor alpha-treated cells suggesting that pX-HBXAP functional collaboration localized downstream to the NF-kappaB nuclear import. Collectively our data suggest that pX recruits and potentiates a novel putative transcription coactivator to regulate NF-kappaB. The implication of pX-HBXAP interaction in the development of hepatocellular carcinoma is discussed.
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PMID:Hepatitis B virus pX interacts with HBXAP, a PHD finger protein to coactivate transcription. 1178 98

Infection of HeLa cells with poliovirus leads to rapid shut-off of host cell transcription by RNA polymerase II. Previous results have suggested that both the basal transcription factor TBP (TATA-binding protein) and transcription activator proteins such as CREB (cyclic AMP-responsive element-binding protein) and Oct-1 (the octamer-binding factor) are cleaved by the viral-encoded protease, 3C(Pro). Here we demonstrate that the transcriptional activator (and tumor suppressor) p53 is degraded by the viral protease 3C both in vivo and in vitro. Unlike other transcription factors that are directly cleaved by 3C(pro), degradation of p53 requires a HeLa cell activity in addition to 3C(Pro). The degradation of p53 by 3C(Pro) does not appear to involve the ubiquitin pathway of protein degradation. Vaccinia virus infection of HeLa cells leads to inactivation of the cellular activity required for 3C(Pro)-mediated degradation of p53. The vaccinia-encoded protein (CrmA) is known to inhibit caspase I (ICE protease) that converts inactive IL-1beta to an active secreted form. Incubation of HeLa cells with caspase I inhibitor Z-VAD-fmk does not interfere with 3C(Pro)-mediated degradation of p53. The cellular activity present in extracts of HeLa cells can be fractionated through phosphocellulose. A partially purified fraction that elutes at 0.6 M KCl from phosphocellulose contains the activity that degrades p53 in a 3C(Pro)-dependent manner. These results suggest that both poliovirus-encoded protease 3C(Pro) and a cellular activity are required for the degradation of p53 observed in cells infected with poliovirus.
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PMID:Poliovirus 3C protease-mediated degradation of transcriptional activator p53 requires a cellular activity. 1187 95

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


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