Dataset Information

Yeast transcription factor Msn2 binds to G4 DNA.

ABSTRACT: Sequences capable of forming quadruplex or G4 DNA are prevalent in the promoter regions. The transformation from canonical to non-canonical secondary structure apparently regulates transcription of a number of human genes. In the budding yeast Saccharomyces cerevisiae, we identified 37 genes with a G4 motif in the promoters including 20 genes that contain stress response element (STRE) overlapping a G4 motif. STRE is the binding site of stress response regulators Msn2 and Msn4, transcription factors belonging to the C2H2 zinc-finger protein family. We show here that Msn2 binds directly to the G4 DNA structure through its zinc-finger domain with a dissociation constant similar to that of STRE-binding and that, in a stress condition, Msn2 is enriched at G4 DNA-forming loci in the yeast genome. For a large fraction of genes with G4/STRE-containing promoters, treating with G4-ligands led to significant elevations in transcription levels. Such transcriptional elevation was greatly diminished in a msn2Δ msn4Δ background and was partly muted when the G4 motif was disrupted. Taken together, our data suggest that G4 DNA could be an alternative binding site of Msn2 in addition to STRE, and that G4 DNA formation could be an important element of transcriptional regulation in yeast.

SUBMITTER: Duy DL

PROVIDER: S-EPMC10570036 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Yeast transcription factor Msn2 binds to G4 DNA.

Duy Duong Long DL Kim Nayun N

Nucleic acids research 20231001 18

Sequences capable of forming quadruplex or G4 DNA are prevalent in the promoter regions. The transformation from canonical to non-canonical secondary structure apparently regulates transcription of a number of human genes. In the budding yeast Saccharomyces cerevisiae, we identified 37 genes with a G4 motif in the promoters including 20 genes that contain stress response element (STRE) overlapping a G4 motif. STRE is the binding site of stress response regulators Msn2 and Msn4, transcription fac ...[more]

PMID: 37615577

Similar Datasets

Project description:Stress induces oscillatory nucleocytoplasmic shuttling of the transcription factor Msn2 in yeast. The subcellular localization of Msn2 is controlled by the cAMP-dependent protein kinase, PKA. Recent experimental observations corroborated by a deterministic computational model for the cAMP-PKA pathway in yeast suggest that the oscillatory dynamics of Msn2 results from the periodic activation of PKA associated with stress-induced oscillations in the level of cAMP. The model accounts for the occurrence of oscillations of Msn2 in a window bounded by two critical values of the stress intensity. In contrast to the rather irregular oscillatory behaviour observed within single yeast cells by means of fluorescence measurements, the deterministic model can only produce a regular pattern of oscillations. To investigate whether the experimentally observed variability could be explained by molecular noise due to the small number of molecules involved in the oscillatory mechanism, we examine a stochastic version of the model for periodic nucleocytoplasmic shuttling of Msn2 coupled to oscillations in the cAMP-PKA pathway. The results of stochastic simulations compare well to the irregular oscillations observed experimentally in the nucleocytoplasmic shuttling of Msn2 in individual yeast cells. The stochastic model retains the property of oscillations within a range bounded by two critical values of stress intensity. We determine the dynamic behaviour as a function of this control parameter and show that the effect of noise markedly depends on the distance from the bifurcation points in the domain of oscillatory behaviour. Finally, we assess the role played by thresholds due to zero-order ultrasensitivity in phosphorylation-dephosphorylation cycles, both in the cAMP-PKA pathway and in the reactions controlling nucleocytoplasmic shuttling of Msn2. In regard to these thresholds, stochastic simulations show that large-amplitude variations of Msn2 associated with large-amplitude oscillations in cAMP can occur outside the domain of sustained oscillations predicted by the deterministic approach.

Dataset Information

Yeast transcription factor Msn2 binds to G4 DNA.

Publications

Yeast transcription factor Msn2 binds to G4 DNA.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets