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

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

Expression of the GAL genes of Saccharomyces cerevisiae is induced during growth on galactose by a well-characterized regulatory mechanism that relieves Gal80p inhibition of the Gal4p transcriptional activator. Growth on glucose overrides induction by galactose. Glucose repression acts at three levels to reduce GAL1 expression: (i) it reduces the level of functional inducer in the cell; (ii) it lowers cellular levels of Gal4p by repressing GAL4 transcription; and (iii) it inhibits Gal4p function through a repression element in the GAL1 promoter. We quantified the amount of repression provided by each mechanism by assaying strains with none, one, two, or all three of the repression mechanisms intact. In a strain lacking all three repression mechanisms, there was almost no glucose repression of GAL1 expression, suggesting that these are the major, possibly the only, mechanisms of glucose repression acting upon the GAL genes. The mechanism of repression that acts to reduce Gal4p levels in the cell is established slowly (hours after glucose addition), probably because Gal4p is stable. By contrast, the repression acting through the upstream repression sequence element in the GAL1 promoter is established rapidly (within minutes of glucose addition). Thus, these three mechanisms of repression collaborate to repress GAL1 expression rapidly and stringently. The Mig1p repressor is responsible for most (possibly all) of these repression mechanisms. We show that for GAL1 expression, mig1 mutations are epistatic to snf1 mutations, indicating that Mig1p acts after the Snf1p protein kinase in the glucose repression pathway, which suggests that Snf1p is an inhibitor of Mig1p.
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PMID:Multiple mechanisms provide rapid and stringent glucose repression of GAL gene expression in Saccharomyces cerevisiae. 819 26

The Saccharomyces cerevisiae GAL2 gene upstream activator sequence (UAS) region was examined for protein bound in vivo by chromatin footprinting at high resolution. Gal4 transcriptional activator protein binds to the two consensus UAS sites whether GAL2 expression is induced, uninduced, or repressed by growth with different carbon sources. Although wild type strains show loss of the Gal4 protein-specific footprint in repressing media containing glucose, constitutive high level expression of Gal4 protein restores the GAL2 UAS footprints without fully derepressing GAL2 transcription. Thus binding of the Gal4 activator to target sites in the DNA is required but not sufficient for GAL2 derepression and induction. Gal4-independent protein-DNA complexes were also detected in the region, including one over the previously noted centromere-binding protein (CP1) site upstream of the Gal4 complexes.
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PMID:Gal4 protein binding is required but not sufficient for derepression and induction of GAL2 expression. 822 24

We cloned the GAL80 gene encoding the negative regulator of the transcriptional activator Gal4 (Lac9) from the yeast Kluyveromyces lactis. The deduced amino acid sequence of K. lactis GAL80 revealed a strong structural conservation between K. lactis Gal80 and the homologous Saccharomyces cerevisiae protein, with an overall identity of 60% and two conserved blocks with over 80% identical residues. K. lactis gal80 disruption mutants show constitutive expression of the lactose/galactose metabolic genes, confirming that K. lactis Gal80 functions in essentially in the same way as does S. cerevisiae Gal80, blocking activation by the transcriptional activator Lac9 (K. lactis Gal4) in the absence of an inducing sugar. However, in contrast to S. cerevisiae, in which Gal4-dependent activation is strongly inhibited by glucose even in a gal80 mutant, glucose repressibility is almost completely lost in gal80 mutants of K. lactis. Indirect evidence suggests that this difference in phenotype is due to a higher activator concentration in K. lactis which is able to overcome glucose repression. Expression of the K. lactis GAL80 gene is controlled by Lac9. Two high-affinity binding sites in the GAL80 promoter mediate a 70-fold induction by galactose and hence negative autoregulation by Gal80. Gal80 in turn not only controls Lac9 activity but also has a moderate influence on its rate of synthesis. Thus, a feedback control mechanism exists between the positive and negative regulators. By mutating the Lac9 binding sites of the GAL80 promoter, we could show that induction of GAL80 is required to prevent activation of the lactose/galactose regulon in glycerol or glucose plus galactose, whereas the noninduced level of Gal80 is sufficient to completely block Lac9 function in glucose.
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PMID:Gal80 proteins of Kluyveromyces lactis and Saccharomyces cerevisiae are highly conserved but contribute differently to glucose repression of the galactose regulon. 824 73

Studies in vivo and in vitro have shown that the packaging of DNA into chromatin can affect gene expression. Here, binding of the yeast transcriptional activator GAL4 to DNA in chromatin has been investigated in vivo with a yeast episome. A positioned nucleosome that is present in cells grown in glucose and contains a single GAL4 binding site is disrupted by GAL4 binding in galactose. GAL4 can also bind to DNA in chromatin when the carboxyl-terminal activation domain of GAL4 is either masked by GAL80 or is absent. These results show that a transcription factor can bind to its site in vivo in what would appear to be a repressive chromatin structure.
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PMID:Nucleosome disruption by transcription factor binding in yeast. 824 5

The yeast transcriptional activator ADR1 is required for expression of the glucose-repressible alcohol dehydrogenase gene (ADH2), as well as genes involved in glycerol metabolism. The N-terminal half of the ADR1 protein was shown to contain three separate transactivation domains, including one (TADI) that encompasses the zinc finger DNA-binding domain. While TADII and TADIII were shown to be functionally redundant in activating ADH2 expression, deletion of only TADIII impaired ADR1 control of glycerol metabolism genes. None of these activation domains appeared to be carbon source regulated when separated from the ADH2 promoter context. Interspersed among these activation domains were two regions which, when removed, increased ADR1 activity; one was localized to the site of ADR1c mutations (residues 227 to 239) that allow glucose-insensitive ADH2 expression. The 227-to-239 region blocked ADR1 activity independently of the TAD present on ADR1, ADR1 DNA binding, and specific ADH2 promoter sequences. In addition, this region inhibited the function of a heterologous transcriptional activator. These results are consistent with the existence of an extragenic factor that binds the ADR1c region and represses ADR1 activity and suggest that other factors are responsible for aiding ADR1 in the carbon source regulation of ADH2.
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PMID:Dissection of the ADR1 protein reveals multiple, functionally redundant activation domains interspersed with inhibitory regions: evidence for a repressor binding to the ADR1c region. 826 31

Glucose repression of the ADH2 gene from Saccharomyces cerevisiae is mediated by the synthesis and activity of the transcriptional activator ADR1. In this study, we isolated mutations in three new genes (SAF1, SAF2 and SAF3) that suppressed the glucose-insensitive expression of ADH2 caused by the ADR1-5c allele. The mechanism by which the SAF genes maintain ADR1-5c function was investigated. Each of the mutated SAF genes was found to suppress ADR1-5c activity by lowering ADR1-5c steady state mRNA levels 5- to 8-fold under glucose growth conditions. ADR1 mRNA levels were similarly affected by the saf mutations. In contrast, mutations in the SAF genes had little or no effect on ADR1-5c or ADR1 mRNA levels under ethanol growth conditions. The stability of ADR1-5c mRNA was unaffected by mutations in each of the SAF genes, implying that the SAF genes are required for the transcription of ADR1 mRNA under glucose growth conditions. The possible function of the three SAF genes in ADR1 expression is discussed.
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PMID:Identification of three genes required for the glucose-dependent transcription of the yeast transcriptional activator ADR1. 843 48

In the budding yeast Kluyveromyces lactis glucose repression of genes involved in lactose and galactose metabolism is primarily mediated by LAC9 (or K1GAL4) the homologue of the well-known Saccharomyces cerevisiae transcriptional activator GAL4. Phenotypic difference in glucose repression existing between natural strains are due to differences in the LAC9 gene (Breunig, 1989, Mol.Gen.Genet. 261, 422-427). Comparison between the LAC9 alleles of repressible and non-repressible strains revealed that the phenotype is a result of differences in LAC9 gene expression. A two-basepair alteration in the LAC9 promoter region produces a promoter-down effect resulting in slightly reduced LAC9 protein levels under all growth conditions tested. In glucose/galactose medium any change in LAC9 expression drastically affects expression of LAC9 controlled genes e.g. those encoding beta-galactosidase or galactokinase revealing a strong dependence of the kinetics of induction on the LAC9 concentration. We propose that in tightly repressible strains the activator concentration drops below a critical threshold that is required for induction to occur. A model is presented to explain how small differences in activator levels are amplified to produce big changes in expression levels of metabolic genes.
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PMID:Glucose repression of lactose/galactose metabolism in Kluyveromyces lactis is determined by the concentration of the transcriptional activator LAC9 (K1GAL4) [corrected]. 844 21

The Saccharomyces cerevisiae transcriptional activator GAL4 is regulated by the presence of available carbon sources. Galactose induces activity by inhibiting the negative regulator GAL80, while glucose, the preferred carbon source, antagonizes GAL4 function by several mechanisms. In the present study we present evidence that one mechanisms for inhibition of GAL transcription by glucose involves direct inhibition of the GAL4 protein. We demonstrate that a large, previously uncharacterized, central region of GAL4 contains at least three 'inhibitory domains' and a 'glucose response domain' (GRD). Deletion of the entire central region eliminates direct inhibition of GAL4 by glucose, and furthermore, fusion of the central region to a heterologous transcriptional activator confers inhibition by glucose. The central region inhibitory domains constitutively inhibit transcriptional activation when the GRD is absent. Direct inhibition of GAL4 activity can be detected within 30 min following glucose addition and may represent an early mechanism promoting a switch from galactose to glucose utilization. A model for the regulatory role of the central region is presented, involving interaction with an additional protein that inhibits GAL4 activity when glucose is present.
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PMID:GAL4 is regulated by a glucose-responsive functional domain. 846 96

The concentration of the transcriptional activator LAC9 (KlGAL4) of Kluyveromyces lactis is moderately regulated by the carbon source as is the case for GAL4, its homolog in Saccharomyces cerevisiae. Expression of the LAC9 gene is induced about twofold in galactose. This induction is due to autoregulation. The LAC9 gene product binds to a low-affinity binding site in the LAC9 promoter and moderately activates transcription in response to galactose above a basal level. As for the LAC9-controlled metabolic genes, induction of LAC9 is inhibited in the presence of glucose. This inhibition of induction is a prerequisite for glucose repression of the lactose-galactose metabolic pathway. On the other hand, induced LAC9 levels are required for optimal growth on galactose, since mutating the LAC9 binding site in the LAC9 promoter resulted in poor growth and reduced expression of LAC9-controlled genes. Thus, in addition to the GAL80-dependent regulation by protein-protein interaction, the regulation of LAC9 gene expression is an important parameter in determining carbon source control of the LAC-GAL regulon. Although the mode of control is different, the pattern of LAC9 gene regulation resembles that of the S. cerevisiae GAL4 gene, being lower in glucose and glucose-galactose than in galactose.
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PMID:Expression of the transcriptional activator LAC9 (KlGAL4) in Kluyveromyces lactis is controlled by autoregulation. 847 61


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