Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overproduction of Gcn4p in yeast cells resulted in the inhibition of transcription from promoters controlled by the GAL4 or dA:dT elements. We have demonstrated that this effect is mediated through the activation domain of Gcn4p and that the function of the transcriptional activator at the affected promoter is impaired. The inhibitory effect of Gcn4p and that the function of the transcriptional activator at the affected promoter is impaired. The inhibitory effect of Gcn4p on these promoters persisted in yeast strains disrupted for the ADA2 and/or GCN5 genes, whose products are required for only part of the transcriptional activation capacity of Gcn4p and other activators, but was alleviated by overexpression of gamma TFIIB. These results support the hypothesis that general transcription factors become unavailable at certain promoters when an activator is overexpressed and strongly imply the existence of an Ada2p/Gcn5p-independent pathway of communication between acidic activators and the basic transcription machinery. In a genetic screen, we have isolated a mutation which neutralises the squelching effects of Gcn4p. This AFR1-1 (activation function reduced) mutation is dominant, it affects the transcriptional activation properties of a number of activators and results in lethality when combined with a gcn5 disruption. Our results suggest that the AFR1 gene product is involved in the mediation of transcriptional activation.
 ...
PMID:Transcriptional interference caused by GCN4 overexpression reveals multiple interactions mediating transcriptional activation. 760 36

The yeast transcriptional activator ADR1, which is required for ADH2 and peroxisomal gene expression, contains four separable and partially redundant activation domains (TADs). Mutations in ADA2 or GCN5, encoding components of the ADA coactivator complex involved in histone acetylation, severely reduced LexA-ADR1-TAD activation of a LexA-lacZ reporter gene. Similarly, the ability of the wild-type ADR1 gene to activate an ADH2-driven promoter was compromised in strains deleted for ADA2 or GCN5. In contrast, defects in other general transcription cofactors such as CCR4, CAF1/POP2, and SNF/SWI displayed much less or no effect on LexA-ADR1-TAD activation. Using an in vitro protein binding assay, ADA2 and GCN5 were found to specifically contact individual ADR1 TADs. ADA2 could bind TAD II, and GCN5 physically interacted with all four TADs. Both TADs I and IV were also shown to make specific contacts to the C-terminal segment of TFIIB. In contrast, no significant binding to TBP was observed. TAD IV deletion analysis indicated that its ability to bind GCN5 and TFIIB was directly correlated with its ability to activate transcription in vivo. ADR1 TADs appear to make several contacts, which may help explain both their partial redundancy and their varying requirements at different promoters. The contact to and dependence on GCN5, a histone acetyltransferase, suggests that rearrangement of nucleosomes may be one important means by which ADR1 activates transcription.
 ...
PMID:ADR1 activation domains contact the histone acetyltransferase GCN5 and the core transcriptional factor TFIIB. 894 99

The ability of p53 to function as a tumor suppressor is linked to its function as a transcriptional activator, since p53 mutants that do not transactivate are unable to suppress tumor cell growth. Previous studies identified an activation domain in the amino terminal 40 residues of the protein, a region that binds to several general transcription factors and to some oncogene products. For example, mdm-2, a cellular oncoprotein, binds to this region and represses p53 transactivation. Here we describe a new activation domain within the amino terminus of p53 that maps between amino acids 40-83, and whose residues trp-53 and phe-54 are critical for function both in yeast and in mammalian cells. In vivo studies in yeast show that the new activation subdomain, unlike the previously described, is mdm-2 independent. Both p53 activation subdomains (1-40 and 40-83) require the yeast adaptor complex ADA2/ADA3/GCN5 for transcriptional activation. Moreover, since activation by p53 requires GCN5's enzymatic histone acetyltransferase domain, p53 may regulate gene expression by influencing chromatin modification.
 ...
PMID:Two tandem and independent sub-activation domains in the amino terminus of p53 require the adaptor complex for activity. 926 67

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.
 ...
PMID:ADR1-mediated transcriptional activation requires the presence of an intact TFIID complex. 974 3

The Saccharomyces cerevisiae CHA1 gene encodes the catabolic L-serine (L-threonine) dehydratase. We have previously shown that the transcriptional activator protein Cha4p mediates serine/threonine induction of CHA1 expression. We used accessibility to micrococcal nuclease and DNase I to determine the in vivo chromatin structure of the CHA1 chromosomal locus, both in the non-induced state and upon induction. Upon activation, a precisely positioned nucleosome (nuc-1) occluding the TATA box and the transcription start site is removed. A strain devoid of Cha4p showed no chromatin alteration under inducing conditions. Five yeast TBP mutants defective in different steps in activated transcription abolished CHA1 expression, but failed to affect induction-dependent chromatin rearrangement of the promoter region. Progressive truncations of the RNA polymerase II C-terminal domain caused a progressive reduction in CHA1 transcription, but no difference in chromatin remodeling. Analysis of swi1, swi3, snf5 and snf6, as well as gcn5, ada2 and ada3 mutants, suggested that neither the SWI/SNF complex nor the ADA/GCN5 complex is involved in efficient activation and/or remodeling of the CHA1 promoter. Interestingly, in a sir4 deletion strain, repression of CHA1 is partly lost and activator-independent remodeling of nuc-1 is observed. We propose a model for CHA1 activation based on promoter remodeling through interactions of Cha4p with chromatin components other than basal factors and associated proteins.
 ...
PMID:Nucleosome structure of the yeast CHA1 promoter: analysis of activation-dependent chromatin remodeling of an RNA-polymerase-II-transcribed gene in TBP and RNA pol II mutants defective in vivo in response to acidic activators. 977 46

The ARABIDOPSIS CBF transcriptional activators bind to the CRT/DRE regulatory element present in the promoters of many cold-regulated genes and stimulate their transcription. Expression of the CBF1 proteins in yeast activates reporter genes carrying a minimal promoter with the CRT/DRE as an upstream regulatory element. Here we report that this ability of CBF1 is dependent upon the activities of three key components of the yeast Ada and SAGA complexes, namely the histone acetyltransferase (HAT) Gcn5 and the transcriptional adaptor proteins Ada2 and Ada3. This result suggested that CBF1 might function through the action of similar complexes in ARABIDOPSIS In support of this hypothesis we found that ARABIDOPSIS has a homolog of the GCN5 gene and two homologs of ADA2, the first report of multiple ADA2 genes in an organism. The ARABIDOPSIS GCN5 protein has intrinsic HAT activity and can physically interact in vitro with both the ARABIDOPSIS ADA2a and ADA2b proteins. In addition, the CBF1 transcriptional activator can interact with the ARABIDOPSIS GCN5 and ADA2 proteins. We conclude that ARABIDOPSIS encodes HAT-containing adaptor complexes that are related to the Ada and SAGA complexes of yeast and propose that the CBF1 transcriptional activator functions through the action of one or more of these complexes.
 ...
PMID:Transcriptional adaptor and histone acetyltransferase proteins in Arabidopsis and their interactions with CBF1, a transcriptional activator involved in cold-regulated gene expression. 1126 54

Despite major advances in characterizing the eukaryotic transcriptional machinery, the function of promoter-specific transcriptional activators (activators) is still not understood. For example, in no case have the direct in vivo targets of a transcriptional activator been unambiguously identified, nor has it been resolved whether activators have a single essential target or multiple redundant targets. Here we address these issues for the prototype acidic activator yeast Gal4p. Gal4p binds to the upstream activating sequence (UAS) of GAL1 and several other GAL genes and stimulates transcription in the presence of galactose. Previous studies have shown that GAL1 transcription is dependent on the yeast SAGA (Spt/Ada/GCN5/acetyltransferase) complex. Using formaldehyde-based in vivo cross-linking, we show that the Gal4p activation domain recruits SAGA to the GAL1 UAS. If SAGA is not recruited to the UAS, the preinitiation complex (PIC) fails to assemble at the GAL1 core promoter, and transcription does not occur. SAGA, but not other transcription components, is also recruited by the Gal4p activation domain to a plasmid containing minimal Gal4p-binding sites. Recruitment of SAGA by Gal4p and stimulation of PIC assembly is dependent on several SAGA subunits but not the SAGA histone acetyl-transferase (HAT) GCN5. Based on these and other results, we conclude that SAGA is an essential target of Gal4p that, following recruitment to the UAS, facilitates PIC assembly and transcription.
 ...
PMID:SAGA is an essential in vivo target of the yeast acidic activator Gal4p. 1148 88

The role played by histone acetyltransferase (HAT), GCN5, in transcriptional co-activation has been analysed in detail in yeast and mammals. Here, we present the cloning and expression pattern of Zmgcn5, the maize homologue. The enzymatic activity of the recombinant ZmGCN5 was analysed with histone and nucleosome substrates. In situ hybridisation of developing maize kernels using Zmgcn5 as probe shows that the transcript is concentrated in rapidly dividing cells. To investigate the role of ZmGCN5 in the transcription of specific plant genes, direct protein-protein interactions were tested. A cDNA clone encoding a putative interacting partner in GCN5-adapter complexes, ZmADA2, was isolated and the interaction between ZmGCN5 and ZmADA2 was confirmed by a GST-spin down experiment. Co-immunoprecipitation of the plant transcriptional activator Opaque-2 and ZmADA2 in nuclear extracts suggests ADA2/GCN5-containing complexes to mediate transcriptional activation by binding of this bZIP factor. For a more general analysis of the effects of histone acetylation on plant gene expression, 2500 ESTs spotted on filters were hybridised with cDNA probes derived either from maize cell lines treated with Trichostatin A (TSA), or from a transgenic line expressing the ZmGCN5 antisense transcript. Several sequences showing marked changes in abundance were confirmed by RNA blot analysis. Inhibition of histone deacetylation with TSA is accompanied by a decrease in the abundance of ZmGCN5 acetylase protein, but by increases in mRNAs for histones H2A, H2B, H3 and H4. The elevated histone mRNA levels were not reflected in increasing histone protein concentrations, suggesting hyperacetylated histones arising from TSA treatment may be preferentially degraded and substituted by de novo synthesised histones. The ZmGCN5 antisense material showed suppression of the endogenous ZmGCN5 transcript and the profiling analysis revealed increased mRNA levels for H2A, H2B and H4. Furthermore, in the antisense line, a reduction in the amount of the RPD3-type HD1B-I histone deacetylase protein was observed. A model for linked regulation of histone acetylation and histone mRNA transcription is discussed.
 ...
PMID:Alteration of GCN5 levels in maize reveals dynamic responses to manipulating histone acetylation. 1258 4

The Arabidopsis GCN5, ADA2a and ADA2b proteins are homologs of components of several yeast and animal transcriptional coactivator complexes. Previous work has implicated these plant coactivator proteins in the stimulation of cold-regulated gene expression by the transcriptional activator protein CBF1. Surprisingly, protein interaction studies demonstrate that the DNA-binding domain of CBF1 (and of a related protein, TINY), rather than its transcriptional activation domain, can bind directly to the Arabidopsis ADA2 proteins. The ADA2a and ADA2b proteins can also bind directly to GCN5 through their N-terminal regions (comparable to a region previously defined in yeast Ada2) and through previously unmapped regions in the middle of the ADA2 proteins, which bind to the HAT domain of GCN5. The ADA2 proteins enhance the ability of GCN5 to acetylate histones in vitro and enable GCN5 to acetylate nucleosomal histones. Moreover, GCN5 can acetylate the ADA2 proteins at a motif unique to the plant homologs and absent from fungal and animal homologs. We speculate that this modification may represent a novel autoregulatory mechanism for the plant SAGA-like transcriptional coactivator complexes.
 ...
PMID:Physical and functional interactions of Arabidopsis ADA2 transcriptional coactivator proteins with the acetyltransferase GCN5 and with the cold-induced transcription factor CBF1. 1660 59

Virion protein 16 (VP16) of herpes simplex virus type 1 (HSV-1) is a potent transcriptional activator of viral immediate-early (IE) genes. The VP16 activation domain can recruit various transcriptional coactivators to target gene promoters. However, the role of transcriptional coactivators in HSV-1 IE gene expression during lytic infection had not been fully defined. We showed previously that transcriptional coactivators such as the p300 and CBP histone acetyltransferases and the BRM and Brg-1 chromatin remodeling complexes are recruited to viral IE gene promoters in a manner dependent mostly on the presence of the activation domain of VP16. In this study, we tested the hypothesis that these transcriptional coactivators are required for viral IE gene expression during infection of cultured cells. The disrupted expression of the histone acetyltransferases p300, CBP, PCAF, and GCN5 or the BRM and Brg-1 chromatin remodeling complexes did not diminish IE gene expression. Furthermore, IE gene expression was not impaired in cell lines that lack functional p300, or BRM and Brg-1. We also tested whether these coactivators are required for the VP16-dependent induction of IE gene expression from transcriptionally inactive viral genomes associated with high levels of histones in cultured cells. We found that the disruption of coactivators also did not affect IE gene expression in this context. Thus, we conclude that the transcriptional coactivators that can be recruited by VP16 do not contribute significantly to IE gene expression during lytic infection or the induction of IE gene expression from nucleosomal templates in vitro.
 ...
PMID:Transcriptional coactivators are not required for herpes simplex virus type 1 immediate-early gene expression in vitro. 1917 20


1 2 Next >>