Perturbation of the interaction between <scp>Gal4p</scp> and <scp>Gal80p</scp> of the <scp><i>S</i></scp><i>accharomyces cerevisiae</i> <scp>GAL</scp> switch results in altered responses to galactose and glucose

Adhikari, Akshay Kumar Das; Qureshi, Mohd. Tanvir; Kar, Rajesh Kumar; Bhat, Paike Jayadeva

doi:10.1111/mmi.12757

Cited by 14 publications

(10 citation statements)

References 79 publications

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“…4). Similar interactions have been previously described for distinct GAL4-GAL80 allele combinations 10,12,14 . Other suppressor combinations yielding WT-like Inducible or Leaky phenotypes included all pairings of Uninducible GAL3 with Leaky GAL80 variants (Fig.…”

Section: Resultssupporting

confidence: 83%

Harmonious genetic combinations rewire regulatory networks and flip gene essentiality

New

Lehner

2019

Nat Commun

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We lack an understanding of how the full range of genetic variants that occur in individuals can interact. To address this shortcoming, here we combine diverse mutations between genes in a model regulatory network, the galactose (GAL) switch of budding yeast. The effects of thousands of pairs of mutations fall into a limited number of phenotypic classes. While these effects are mostly predictable using simple rules that capture the ‘stereotypical’ genetic interactions of the network, some double mutants have unexpected outcomes including constituting alternative functional switches. Each of these ‘harmonious’ genetic combinations exhibits altered dependency on other regulatory genes. These cases illustrate how both pairwise and higher epistasis determines gene essentiality and how combinations of mutations rewire regulatory networks. Together, our results provide an overview of how broad spectra of mutations interact, how these interactions can be predicted, and how diverse genetic solutions can achieve ‘wild-type’ phenotypic behavior.

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Section: Resultssupporting

confidence: 83%

Harmonious genetic combinations rewire regulatory networks and flip gene essentiality

New

Lehner

2019

Nat Commun

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“…The ancestor, epistatically-altered strain, and the gal3 Δ strains used in this study are as described previously ( Johnston and Hopper, 1982 ; Das Adhikari et al, 2014 ). To measure GAL1 promoter activity in these three strains GAL1-lacZ fusions were integrated at the ura3 locus, as described previously ( Das Adhikari et al, 2014 ).…”

Section: Methodsmentioning

confidence: 99%

“…GAL1-lacZ levels were determined in the three strains, ancestor, the epistatically altered strain, and the gal3 Δ as described previously ( Das Adhikari et al, 2014 ).…”

Section: Methodsmentioning

confidence: 99%

GAL Regulon in the Yeast S. cerevisiae is Highly Evolvable via Acquisition in the Coding Regions of the Regulatory Elements of the Network

Rajeshkannan

Mahilkar

Saini

2022

Front. Mol. Biosci.

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GAL network in the yeast S. cerevisiae is one of the most well-characterized regulatory network. Expression of GAL genes is contingent on exposure to galactose, and an appropriate combination of the alleles of the regulatory genes GAL3, GAL1, GAL80, and GAL4. The presence of multiple regulators in the GAL network makes it unique, as compared to the many sugar utilization networks studied in bacteria. For example, utilization of lactose is controlled by a single regulator LacI, in E. coli’s lac operon. Moreover, recent work has demonstrated that multiple alleles of these regulatory proteins are present in yeast isolated from ecological niches. In this work, we develop a mathematical model, and demonstrate via deterministic and stochastic runs of the model, that behavior/gene expression patterns of the cells (at a population level, and at a single-cell resolution) can be modulated by altering the binding affinities between the regulatory proteins. This adaptability is likely the key to explaining the multiple GAL regulatory alleles discovered in ecological isolates in recent years.

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“…The genes required for utilization of galactose ( GAL ) in yeast have served as an important model for understanding mechanisms of transcriptional regulation in eukaryotes ( Das Adhikari et al 2014 ). The GAL genes are activated by Gal4, which in the absence of galactose is inhibited by interaction with Gal80 ( Li et al 2010 ).…”

Section: Introductionmentioning

confidence: 99%

TORC1 signaling modulates Cdk8-dependent GAL gene expression in Saccharomyces cerevisiae

et al. 2021

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Cdk8 of the RNA Polymerase II mediator kinase complex regulates gene expression by phosphorylating sequence-specific transcription factors. This function is conserved amongst eukaryotes, but the signals and mechanisms regulating Cdk8 activity and phosphorylation of its substrates are unknown. Full induction of the GAL genes in yeast requires phosphorylation of the transcriptional activator Gal4 by Cdk8. We used a screen to identify regulators of the Cdk8-dependent phosphorylation on Gal4, from which we identified multiple mutants with defects in TORC1 signaling. One mutant, designated gal four throttle 1 (gft1) was identified as a recessive allele of hom3, encoding aspartokinase, and mutations in hom3 caused effects typical of inhibition of TORC1, including rapamycin sensitivity and enhanced nuclear localization of the TORC1-responsive transcription factor Gat1. Mutations in hom3 also inhibit phosphorylation of Gal4 in vivo at the Cdk8-dependent site on Gal4, as did mutations of tor1, but these mutations did not affect activity of Cdk8 assayed in vitro. Disruption of cdc55, encoding a regulatory subunit of the TORC1-regulated protein phosphatase PP2A, suppressed the effect of hom3 and tor1 mutations on GAL expression, and also restored phosphorylation of Gal4 at the Cdk8-dependent site in vivo. These observations demonstrate that TORC1 signaling regulates GAL induction through the activity of PP2A/Cdc55, and suggest that Cdk8-dependent phosphorylation of Gal4 is opposed by PP2A/Cdc55 dephosphorylation. These results provide insight into how induction of transcription by a specific inducer can be modulated by global nutritional signals through regulation of Cdk8-dependent phosphorylation.

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Perturbation of the interaction between Gal4p and Gal80p of the Saccharomyces cerevisiae GAL switch results in altered responses to galactose and glucose

Cited by 14 publications

References 79 publications

Harmonious genetic combinations rewire regulatory networks and flip gene essentiality

Harmonious genetic combinations rewire regulatory networks and flip gene essentiality

GAL Regulon in the Yeast S. cerevisiae is Highly Evolvable via Acquisition in the Coding Regions of the Regulatory Elements of the Network

TORC1 signaling modulates Cdk8-dependent GAL gene expression in Saccharomyces cerevisiae

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