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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 transcriptional activator GAL4 binds co-operatively to four related 17-base-pair sequences within an upstream activating sequence (UASG) to activate transcription of the GAL1 and GAL10 genes. It belongs to a class of gene regulatory proteins which all contain a highly conserved cysteine-rich region within their DNA-binding domains. This region binds zinc and it has been proposed that the cysteine residues coordinate the zinc, creating a structure analogous to one of the 'zinc fingers' of the transcription factor TFIIIA (ref. 8). Using 1H-113Cd two-dimensional nuclear magnetic resonance spectra of the cadmium form of the domain, we previously showed that the protein contains a Cd2Cys6 cluster where cysteines 11 and 28 act as bridging ligands. A similar study of a fragment of GAL4 has recently been published. We report here the solution structure of the DNA binding domain of GAL4; two helix-turn-strand motifs pack around a Zn2Cys6 cluster in a novel pseudo-symmetrical arrangement. The results show that the GAL4 zinc-binding domain differs significantly from both the TFIIIA-type zinc finger and the steroid hormone receptor DNA-binding domains.
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PMID:Structure of the DNA-binding domain of zinc GAL4. 155 14

An in vivo selection system for isolating targets of DNA binding proteins in yeast was developed and used to identify the DNA binding site for the NGFI-B protein, a member of the steroid-thyroid hormone receptor superfamily. The feasibility of the technique was verified by selecting DNA fragments that contained binding sites for GCN4, a well-characterized yeast transcriptional activator. The DNA binding domain of NGFI-B, expressed as part of a LexA-NGFI-B-GAL4 chimeric activator, was then used to isolate a rat genomic DNA fragment that contained an NGFI-B binding site. The NGFI-B response element (NBRE) is similar to but functionally distinct from elements recognized by the estrogen and thyroid hormone receptors and the hormone receptor-like proteins COUP-TF, CF1, and H-2RIIBP. Cotransfection experiments in mammalian cells demonstrated that NGFI-B can activate transcription from the NBRE with or without its putative ligand binding domain.
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PMID:Identification of the DNA binding site for NGFI-B by genetic selection in yeast. 192 41

RAP1 is a sequence-specific DNA-binding protein essential for cell growth. The occurrence of RAP1-binding sites in many promoter regions, the mating-type gene silencer elements, and telomeres suggests that RAP1 has multiple functions in the cell. To assess its role in transcription, temperature-sensitive mutations in RAP1 were generated. Analysis of rap1ts strains provides evidence that RAP1 functions in both transcriptional activation and silencing of mating-type genes. Several observations indicate that rap1ts strains are defective in the expression of MAT alpha, whose upstream activation sequence (UAS) contains a RAP1-binding site. At nonpermissive temperatures, decreases in MAT alpha steady-state transcript levels can be detected in MAT alpha rap1ts strains. Furthermore, these strains are deficient in alpha-pheromone production and simultaneously express at least two alpha-specific genes. These phenotypes can be reversed by replacing the RAP1-binding site at MAT alpha with a binding site for the GAL4 transcriptional activator. Certain rap1ts alleles have an opposite effect on the silent mating-type locus HMR, which becomes partially derepressed at nonpermissive temperatures.
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PMID:RAP1 protein activates and silences transcription of mating-type genes in yeast. 201 87

Endogenous mouse mammary tumor virus (MMTV) proviral transcripts are up regulated during the normal course of B-lymphocyte differentiation. We report here that the regulatory mechanisms which lead to increased levels of MMTV transcripts in differentiating, lipopolysaccharide (LPS)-stimulated normal B cells and in the inducible B-cell lymphoma line CH12 are at least partially distinct from those controlling increases in immunoglobulin and J-chain gene expression. In studies designed to characterize the stimulatory pathways leading to MMTV expression in CH12 cells, we found that stimulation with either LPS or dexamethasone (Dex), a transcriptional activator of MMTV genes, induced not only MMTV expression but also differentiation to antibody secretion. Only Dex-induced and not LPS-induced MMTV expression and differentiation were inhibited by the glucocorticoid antagonist RU486, demonstrating that Dex and LPS stimulate B cells by distinct molecular pathways. Therefore, in B cells, MMTV expression can be regulated via either the conventional hormone receptor-dependent pathway or a hormone receptor-independent pathway. Furthermore, these results suggest that steroid stimulation of B cells can lead to alterations in the expression of other results suggest that steroid stimulation of B cells can lead to alterations in the expression of other steroid-responsive genes that can become involved in the process of B-cell differentiation.
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PMID:Lipopolysaccharide and dexamethasone induce mouse mammary tumor proviral gene expression and differentiation in B lymphocytes through distinct regulatory pathways. 216 35

Upstream sequences of the Klebsiella pneumoniae nifH promoter were mutagenised and activation of the mutated promoters by the nif-specific transcriptional activator protein NifA examined in vivo. Of the sixteen mutations analysed, only those within the nifH upstream activator sequence (UAS), characterised by a TGT-N10-ACA motif, influenced nifH promoter activity. Mutations altering the two-fold rotational symmetry of the UAS or the spacing between the TGT and ACA motifs reduced promoter activity, consistent with the UAS functioning as a NifA binding site. The bases flanking the TGT-ACA motif of the UAS also appear to influence activation by NifA. Substituting the nifH UAS with a binding site for the transcriptional activator NtrC resulted in improved NtrC-dependent activation of the nifH promoter demonstrating that the activator specificity of the nifH promoter is dependent upon the presence of the appropriate upstream sequences to which the activator binds.
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PMID:Mutational analysis of upstream sequences required for transcriptional activation of the Klebsiella pneumoniae nifH promoter. 332 Sep 58

The biological response to progesterone is mediated by two distinct forms of the human progesterone receptor (hPR-A and hPR-B). In most cell contexts, hPR-B functions as a transcriptional activator of progesterone-responsive genes, whereas hPR-A functions as a transcriptional inhibitor of all steroid hormone receptors. We have created mutations within the carboxyl terminus of hPR which differentially effect the transcriptional activity of hPR-B in a cell- and promoter-specific manner. Analogous mutations, when introduced into hPR-A, have no effect on its ability to inhibit the transcriptional activity of other steroid hormone receptors. The observed differences in the structural requirements for hPR-B and hPR-A function suggest that transcriptional activation and repression by PR are mediated by two separate pathways within the cell. In support of this hypothesis, we have shown that hPR-A mediated repression of human estrogen receptor (hER) transcriptional activity is not dependent on hER expression level but depends largely on the absolute expression level of hPR-A. Thus, it appears that hPR-A inhibits hER transcriptional activity as a consequence of a noncompetitive interaction of hPR-A with either distinct cellular targets or different contact sites on the same target. We propose that hPR-A expression facilitates a ligand-dependent cross-talk among sex steroid receptor signaling pathways within the cell. It is likely, therefore, that alterations in the expression level of hPR-A or its cellular target can have profound effects on the physiological or pharmacological responses to sex steroid hormone receptor ligands.
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PMID:The A and B isoforms of the human progesterone receptor operate through distinct signaling pathways within target cells. 796 70

Hepatocyte nuclear factor 4 (HNF-4), found in liver, kidney, and intestine, is a potent transcriptional activator that controls the expression of a wide variety of genes, including those involved in fatty acid and cholesterol metabolism, glucose metabolism, urea biosynthesis, blood coagulation, hepatitis B infections, and liver differentiation. HNF-4 is also a member of the steroid hormone receptor superfamily and has been highly conserved throughout evolution, suggesting that it might respond to an as yet unidentified ligand. In this presentation, some of the current findings regarding the role of HNF-4 in liver-specific gene expression are reviewed.
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PMID:Orphan receptor HNF-4 and liver-specific gene expression. 803 8

The CDC68 gene (also called SPT16) encodes a transcription factor for the expression of a diverse set of genes in the budding yeast Saccharomyces cerevisiae. To identify other proteins that are functionally related to the Cdc68 protein, we searched for genetic suppressors of a cdc68 mutation. Four suppressor genes in which mutations reverse the temperature sensitivity imposed by the cdc68-1 mutation were found. We show here that one of the suppressor genes is the previously reported SAN1 gene; san1 mutations were originally identified as suppressors of a sir4 mutation, implicated in the chromatin-mediated transcriptional silencing of the two mating-type loci HML and HMR. Each san1 mutation, including a san1 null allele, reversed all aspects of the cdc68 mutant phenotype. Conversely, increased copy number of the wild-type SAN1 gene lowered the restrictive temperature for the cdc68-1 mutation. Our findings suggest that the San1 protein antagonizes the transcriptional activator function of the Cdc68 protein. The identification of san1 mutations as suppressors of cdc68 mutations suggests a role for Cdc68 in chromatin structure.
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PMID:The Saccharomyces cerevisiae Cdc68 transcription activator is antagonized by San1, a protein implicated in transcriptional silencing. 824 72

Rev-ErbA alpha (Rev-Erb) is a nuclear hormone receptor-related protein encoded on the opposite strand of the alpha-thyroid hormone receptor (TR) gene. This unusual genomic arrangement may have a regulatory role, but the conservation of human and rodent Rev-Erb amino acid sequences suggests that the protein itself has an important function, potentially as a sequence-specific transcriptional regulator. However, despite its relationship to the TR, Rev-Erb bound poorly to TR binding sites. To determine its DNA-binding specificity in an unbiased manner, Rev-Erb was synthesized in Escherichia coli, purified, and used to select specific binding-sites from libraries of random double-stranded DNA sequences. We found that Rev-Erb binds to a unique site consisting of a specific 5-bp A/T-rich sequence adjacent to a TR half-site. Rev-Erb contacts this entire asymmetric 11-bp sequence, which is the longest nonrepetitive element specifically recognized by a member of the thyroid/steroid hormone receptor superfamily, and mutations in either the A/T-rich or TR half-site regions abolished specific binding. The binding specificity of wild-type Rev-Erb was nearly identical to that of C- and N-terminally truncated forms. This binding was not enhanced by retinoid X receptor, TR, or other nuclear proteins, none of which formed heterodimers with Rev-Erb. Rev-Erb also appeared to bind to the selected site as a monomer. Furthermore, Rev-Erb activates transcription through this binding site even in the absence of exogenous ligand. Thus, Rev-Erb is a transcriptional activator whose properties differ dramatically from those of classical nuclear hormone receptors, including the TR encoded on the opposite strand of the same genomic locus.
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PMID:The orphan receptor Rev-ErbA alpha activates transcription via a novel response element. 847 64

Homothallic strains of Saccharomyces cerevisiae can change mating type as often as every generation by replacing the allele at the MAT locus with a copy of mating type information present at one of two storage loci, HML and HMR, located on either end of chromosome III. Selection of the appropriate donor locus is dictated by a mating type-specific repressor protein, alpha2p: Cells containing alpha2p select HMR, whereas those lacking alpha2p select HML. As a repressor protein, alpha2p binds to DNA cooperatively with the transcriptional activator Mcm1p. Here we show that two alpha2p/Mcm1p-binding sites, DPS1 and DPS2, control donor selection. DPS1 and DPS2 are located approximately 30 kb from the left arm of chromosome III, well removed from HML, HMR, and MAT. Precise deletion of only DPS1 and DPS2 results in random selection of donor loci and in a cells without affecting selection in alpha cells. Reciprocally, deletion of only the alpha2p binding segments in each of these two sites results in selection of the wrong donor loci in alpha cells without affecting preference in a cells. These results suggest that Mcm1p, bound to these two sites in the absence of alpha2p, activates HML as donor. Binding of alpha2p blocks the ability of Mcm1p bound to DPS1 and DPS2 to activate HML, resulting in default selection of HMR as donor. DPS1 and DPS2 also regulate expression of several noncoding RNAs, although deletion of at least one of these RNA loci does not affect donor preference. This suggests that transcriptional activation, rather than transcription of a specific product, is the initiating event in activating the left arm of chromosome III for donor selection.
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PMID:Alpha2p controls donor preference during mating type interconversion in yeast by inactivating a recombinational enhancer of chromosome III. 927 Nov 14


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