In Vitro Transcriptional Activation by a Metabolic Intermediate: Activation by Leu3 Depends on α-Isopropylmalate

Sze, Ji Ying; Woontner, Michael; Jaehning, Judith A.; Kohlhaw, Gunter B.

doi:10.1126/science.1439822

Cited by 94 publications

(96 citation statements)

References 17 publications

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“…Activity of a number of zinc cluster proteins is controlled by intermediary metabolites (for a review, see Sellick and Reece 2005). For example, the activity of the zinc cluster proteins Leu3 and Lys14 is controlled by intermediary metabolites of leucine and lysine biosynthesis, respectively (Feller et al 1994;Feller et al 1999;Sze et al 1992). In contrast, our unpublished results showed that activation by Uga3 is not dependent on the presence of GABA metabolites since no reduction of reporter activity is observed in strains Duga1 and Duga2, which are unable to catabolize GABA.…”

Section: Discussioncontrasting

confidence: 48%

Yeast Zinc Cluster Proteins Dal81 and Uga3 Cooperate by Targeting Common Coactivators for Transcriptional Activation of Γ-Aminobutyrate Responsive Genes

Sylvain¹,

Liang²,

Hellauer³

et al. 2011

Genetics

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In Saccharomyces cerevisiae, optimal utilization of various compounds as a nitrogen source is mediated by a complex transcriptional network. The zinc cluster protein Dal81 is a general activator of nitrogen metabolic genes, including those for g-aminobutyrate (GABA). In contrast, Uga3 (another zinc cluster protein) is an activator restricted to the control of genes involved in utilization of GABA. Uga3 binds to DNA elements found in the promoters of target genes and increases their expression in the presence of GABA. Dal81 appears to act as a coactivator since the DNA-binding activity of this factor is dispensable but its mode of action is not known. In this study, we have mapped a regulatory, as well as an activating, region for Uga3. A LexA-Uga3 chimeric protein activates a lexA reporter in a GABA-and Dal81-dependent manner. Activation by Uga3 requires the SAGA complex as well as Gal11, a component of mediator. ChIP analysis revealed that Uga3 is weakly bound to target promoters. The presence of GABA enhances binding of Uga3 and allows recruitment of Dal81 and Gal11 to target genes. Recruitment of Gal11 is prevented in the absence of Dal81. Importantly, Dal81 by itself is a potent activator when tethered to DNA and its activity depends on SAGA and Gal11 but not Uga3. Overexpression of Uga3 bypasses the requirement for Dal81 but not for SAGA or Gal11. Thus, under artificial conditions, both Dal81 and Uga3 can activate transcription independently of each other. However, under physiological conditions, both factors cooperate by targeting common coactivators.

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Section: Discussioncontrasting

confidence: 48%

Yeast Zinc Cluster Proteins Dal81 and Uga3 Cooperate by Targeting Common Coactivators for Transcriptional Activation of Γ-Aminobutyrate Responsive Genes

Sylvain¹,

Liang²,

Hellauer³

et al. 2011

Genetics

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“…The recent structural study on Ets-1 suggests that a C-terminal domain interacts within an N-terminal inhibitory region (15). In yeast, Leu3p is transcriptionally active only in the presence of ␣-isopropylmalate (66). A model has been proposed in which interaction of the central part with the C-terminal activation domain prevents activation of Leu3p until an ␣-isopropylmalate-induced conformational change occurs (77).…”

Section: Discussionmentioning

confidence: 99%

The DNA Binding and Activation Domains of Gal4p Are Sufficient for Conveying Its Regulatory Signals

Ding

Johnston

1997

Molecular and Cellular Biology

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The transcriptional activation function of the Saccharomyces cerevisiae activator Gal4p is known to rely on a DNA binding activity at its amino terminus and an activation domain at its carboxy terminus. Although both domains are required for activation, truncated forms of Gal4p containing only these domains activate poorly in vivo. Also, mutations in an internal conserved region of Gal4p inactivate the protein, suggesting that this internal region has some function critical to the activity of Gal4p. We have addressed the question of what is the minimal form of Gal4 protein that can perform all of its known functions. A form with an internal deletion of the internal conserved domain of Gal4p is transcriptionally inactive, allowing selection for suppressors. All suppressors isolated were intragenic alterations that had further amino acid deletions (miniGAL4s). Characterization of the most active miniGal4 proteins demonstrated that they possess all of the known functions of full-length Gal4p, including glucose repression, galactose induction, response to deletions of gal11 or gal6, and interactions with other proteins such as Gal80p, Sug1p, and TATA binding protein. Analysis of the transcriptional activities, protein levels, and DNA binding abilities of these miniGal4ps and a series of defined internal mutants compared to those of the full-length Gal4p indicates that the DNA binding and activation domains are necessary and sufficient qualitatively for all of these known functions of Gal4p. Our observations imply that the internal region of Gal4 protein may serve as a spacer to augment transcription and/or may be involved in intramolecular or Gal4p-Gal4p interactions.

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“…Interestingly, not only isoamyl alcohol and isoamyl acetate increased in this mutant: the production of total diacetyl during fermentation was also about 3 times higher in the mutant CMBSPV03TFL, compared to CMBSPV03. This could be explained by altered expressions, caused by the activated transcriptional factor Leu3p, of ILV2 and ILV5, which encode the α-acetolactate synthase and the α-acetolactate reductoisomerase respectively, as a result of the mutation 31 . The activity of these enzymes determines the production of α-acetolactate during fermentation, which is converted to diacetyl by an oxidative decarboxylation 33 .…”

Section: Impact Of Hd On Flavourmentioning

confidence: 99%

Characteristics of High Cell Density Fermentations with Different Lager Yeast Strains

Verbelen

Mulders

Saison

et al. 2008

Journal of the Institute of Brewing

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To improve the productivity of the beer fermentation process, several strategies can be adopted. One of these promising strategies could be the increase of suspended yeast cells in the reactor. Therefore, the fermentation characteristics of 11 lager yeast strains were studied in normal pitched worts (20 × 10 6 cells/ mL) (LD) and in worts with a four-fold higher pitching rate (HD). The fermentation rate was 2-4 times increased when high initial cell levels were used. The net yeast growth was somewhat similar between the LD and the HD fermentations, although the FAN uptake level was about 35% higher in the HD fermentations compared with LD. High viabilities were observed throughout the fermentations with high cell loadings. HD fermentations resulted in higher concentrations of all the measured fusel alcohols and higher maxima and residual concentrations of total diacetyl were observed. In contrast, higher levels of most of the esters were found at the normal pitching rate, although the results of isoamyl acetate were not significant. With the help of "Principal Component Analysis", it became clear that the cell density had an important influence on the flavour profile, but that yeast specific preferences could not be overlooked as they determined the sensitivity of the yeast to the application of higher cell densities.

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In Vitro Transcriptional Activation by a Metabolic Intermediate: Activation by Leu3 Depends on α-Isopropylmalate

Cited by 94 publications

References 17 publications

Yeast Zinc Cluster Proteins Dal81 and Uga3 Cooperate by Targeting Common Coactivators for Transcriptional Activation of Γ-Aminobutyrate Responsive Genes

Yeast Zinc Cluster Proteins Dal81 and Uga3 Cooperate by Targeting Common Coactivators for Transcriptional Activation of Γ-Aminobutyrate Responsive Genes

The DNA Binding and Activation Domains of Gal4p Are Sufficient for Conveying Its Regulatory Signals

Characteristics of High Cell Density Fermentations with Different Lager Yeast Strains

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