Binding and regulation of transcription by yeast Ste12 variants to drive mating and invasion phenotypes
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ABSTRACT:
PROVIDER: PRJNA595929 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10704114_1.fastq.gz | Fastqsanger.gz | |||
| SRR10704114_2.fastq.gz | Fastqsanger.gz | |||
| SRR10704115_1.fastq.gz | Fastqsanger.gz | |||
| SRR10704115_2.fastq.gz | Fastqsanger.gz | |||
| SRR10704116_1.fastq.gz | Fastqsanger.gz |
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Project description:Here, we examine how six single amino acid variants in the DNA-binding domain of Ste12 – a yeast transcription factor regulating mating and invasion – alter Ste12 genome binding, motif recognition and gene expression to yield markedly different phenotypes. Using a combination of the calling card method, RNA sequencing , we find that variants with dissimilar binding and expression profiles can converge onto similar cellular behaviors.
2020-01-30 | GSE141713 | GEO
Project description:Amino acid substitutions are commonly found in human transcription factors, yet the functional consequences of much of this variation remain unknown, even in well-characterized DNA-binding domains. Here, we examine how six single-amino acid variants in the DNA-binding domain of Ste12-a yeast transcription factor regulating mating and invasion-alter Ste12 genome binding, motif recognition, and gene expression to yield markedly different phenotypes. Using a combination of the "calling-card" method, RNA sequencing, and HT-SELEX (high throughput systematic evolution of ligands by exponential enrichment), we find that variants with dissimilar binding and expression profiles can converge onto similar cellular behaviors. Mating-defective variants led to decreased expression of distinct subsets of genes necessary for mating. Hyper-invasive variants also decreased expression of subsets of genes involved in mating, but increased the expression of other subsets of genes associated with the cellular response to osmotic stress. While single-amino acid changes in the coding region of this transcription factor result in complex regulatory reconfiguration, the major phenotypic consequences for the cell appear to depend on changes in the expression of a small number of genes with related functions.
| S-EPMC7017024 | biostudies-literature
Project description:Cellular processes are subject to variability, or noise, yet mechanisms that promote cell-to-cell uniformity are poorly understood. We have identified such a role for Dig1, a redundant (with Dig2) MAPK-responsive inhibitor of the S. cerevisiae mating pathway transcription factor Ste12. Cells lacking Dig1, but not Dig2, exhibited increased variability in outputs of the mating pathway. dig1∆ mutants also displayed a Ste12-dependent defect in growth in the absence of mating pheromone and a quantitative defect in the process of mating, itself. In cells expressing two reporter genes driven by the same promoter, both intrinsic/uncorrelated and extrinsic/correlated noise were found to increase. Remarkably, the extrinsic noise phenotype in cells lacking Dig1 correlates with the aggregation of target genes: we observed subnuclear foci of Ste12 specifically in dig1∆ cells and, using a newly-developed method to immunoprecipitate a single locus from crosslinked chromatin, we found that Dig1 inhibits long-range interactions between Ste12 target genes in vivo. Dig1 may shield binding surfaces on Ste12 whose unmasking leads to inappropriate gene associations and increased gene expression noise. These studies reveal how investigations of variability modulation mechanisms can yield unexpected biological insights.
2010-12-15 | GSE17583 | GEO
Project description:Cellular processes are subject to variability, or noise, yet mechanisms that promote cell-to-cell uniformity are poorly understood. We have identified such a role for Dig1, a redundant (with Dig2) MAPK-responsive inhibitor of the S. cerevisiae mating pathway transcription factor Ste12. Cells lacking Dig1, but not Dig2, exhibited increased variability in outputs of the mating pathway. dig1∆ mutants also displayed a Ste12-dependent defect in growth in the absence of mating pheromone and a quantitative defect in the process of mating, itself. In cells expressing two reporter genes driven by the same promoter, both intrinsic/uncorrelated and extrinsic/correlated noise were found to increase. Remarkably, the extrinsic noise phenotype in cells lacking Dig1 correlates with the aggregation of target genes: we observed subnuclear foci of Ste12 specifically in dig1∆ cells and, using a newly-developed method to immunoprecipitate a single locus from crosslinked chromatin, we found that Dig1 inhibits long-range interactions between Ste12 target genes in vivo. Dig1 may shield binding surfaces on Ste12 whose unmasking leads to inappropriate gene associations and increased gene expression noise. These studies reveal how investigations of variability modulation mechanisms can yield unexpected biological insights. The FUS1 locus is tagged with an array of lac operators. Wild type and dig1∆ cells containing this tagged FUS1 locus and expressing a mCherry-LacI were grown up for ChIP-chip. The FUS1 locus was selectively immunoprecipitated using an anti-DsRed antibody.
2010-12-15 | E-GEOD-17583 | biostudies-arrayexpress
Project description:A fundamental problem in biology is the molecular basis for divergence among related organisms. We have investigated the level of divergence of transcription factor binding sites for two key factors that regulate developmental processes in the budding yeasts. The genomic binding locations for the Ste12 and Tec1 transcription factors in S. cerevisiae, S. mikatae and S. bayanus were mapped by chromatin immunoprecipitation combined with microarrays (chIP chip)1, 2 and compared to one another. While there was a large core network which was conserved in all three species, there were many instances of binding events whose relative levels differ significantly quantitatively in one species relative to another and as well as species-specific binding events. One interesting class of genes were identified that were bound only in S. mikatae and S. bayanus; many of these genes are targets of Ste12 in haploid strains of S. cerevisiae, suggesting that S. cerevisiae has uniquely acquired the ability to differentially regulate these genes in haploid and diploid cells in these species. To extend these studies, the transcriptional network for the Ste12 homologue (Cph1) in Candida albicans was also mapped and compared to the Saccharomyces species. Again, there were several genes bound by Cph1 which are involved in mating in S. cerevisiae, suggesting that the precise delineation between many mating and pseudohyphal targets by Ste12 may be specific to S. cerevisiae. Overall our results demonstrate that transcription binding sites differ faster than gene content indicating that gene regulation at the level of transcription factor binding is likely to be a major mode of evolutionary divergence between related species. We expect that this divergence is essential for the distinct ecological niches inhabited by these organisms. Keywords: chIP-chip
2007-09-06 | GSE5421 | GEO
Project description:A fundamental problem in biology is the molecular basis for divergence among related organisms. We have investigated the level of divergence of transcription factor binding sites for two key factors that regulate developmental processes in the budding yeasts. The genomic binding locations for the Ste12 and Tec1 transcription factors in S. cerevisiae, S. mikatae and S. bayanus were mapped by chromatin immunoprecipitation combined with microarrays (chIP chip)1, 2 and compared to one another. While there was a large core network which was conserved in all three species, there were many instances of binding events whose relative levels differ significantly quantitatively in one species relative to another and as well as species-specific binding events. One interesting class of genes were identified that were bound only in S. mikatae and S. bayanus; many of these genes are targets of Ste12 in haploid strains of S. cerevisiae, suggesting that S. cerevisiae has uniquely acquired the ability to differentially regulate these genes in haploid and diploid cells in these species. To extend these studies, the transcriptional network for the Ste12 homologue (Cph1) in Candida albicans was also mapped and compared to the Saccharomyces species. Again, there were several genes bound by Cph1 which are involved in mating in S. cerevisiae, suggesting that the precise delineation between many mating and pseudohyphal targets by Ste12 may be specific to S. cerevisiae. Overall our results demonstrate that transcription binding sites differ faster than gene content indicating that gene regulation at the level of transcription factor binding is likely to be a major mode of evolutionary divergence between related species. We expect that this divergence is essential for the distinct ecological niches inhabited by these organisms. Keywords: chIP-chip ChIP-chip was performed on Ste12 and Tec1 from S. cerevisiae, S. mikatae and S. bayanus in addition to Cph1 from S. cerevisiae. Three biological replicates were performed for each factor in each species with one replicate representing a dye swap.
2007-09-06 | E-GEOD-5421 | biostudies-arrayexpress
Project description:Glioblastoma (GBM), the most common primary brain cancer in adults, is characterized by rapid local invasion along diverse routes, such as infiltration of white matter tracts and penetration of perivascular spaces. We investigate the hypothesis that GBM invasion routes correlate with the transcriptional states of individual cells and identify regulators of route-specific invasion. Utilizing patient-derived GBM xenograft models, we integrate single-cell transcriptomics and spatial proteomics, revealing that mesenchymal and oligodendrocyte progenitor-like GBM cells migrate perivascularly, while neural progenitor and astrocyte-like GBM cells invade diffusely. Computational reconstruction identifies ANXA1 as a perivascular invasion driver and lineage-restricted transcription factors RFX4 and HOPX as drivers of diffuse invasion, predictive of patient survival. Genetic ablation of these genes alters invasion phenotypes and extends survival in xenografted mice, clarifying the role of cell states in GBM invasion, and highlighting potential therapeutic targets for selective invasion route targeting in GBM patients.
2025-06-15 | GSE270083 | GEO
Project description:We examined the mating response of three yeast species, by subjecting a-type cells from each of them to alpha-factor (6uM). The expression of cells before and after (60min) addition of alpha-factor were compared using S. cerevisiae cDNA microarrays. In addition, we verified our results with a true mating experiment: the expression of a-type and alpha-type cells from S. cerevisiae were compared before and after mixing them for 90 minutes (i.e. allowing them to mate). Keywords: yeast mating response, comparison among species
2007-05-20 | GSE7525 | GEO
Project description:Yeast chromosome III contains the mating type loci that provide a paradigm for long-range interactions between distant loci. Yeast switch mating type by gene conversion between the MAT locus and either of two silent loci (HML or HMR) on opposite ends of the chromosome. This long-range process is mating type-specific so that MATa cells choose HML as template, while MATα cells use HMR. The Recombination Enhancer (RE), located on the left arm regulates this process. One long-standing hypothesis is that switching is guided by mating type-specific, and possibly RE-dependent three-dimensional folding of chromosome III. Here we used Hi-C, 5C, and live cell imaging to characterize the conformation of chromosome III in both mating types in non-switching strains. We discovered a mating type-specific difference in the folding of the left arm: in MATa cells the left arm is located closely to the centromere-proximal portion of the chromosome as well as to MAT, whereas it is more extended away in MATα cells. Deletion analysis showed that a 1 kb subregion within the RE, which is not necessary during switching, abolished mating type-dependent chromosome folding. In this mutant the conformation of chromosome III is the same in both mating types, but distinct from the wild type MATa or MATα conformations, indicating that the RE induces conformational changes in both mating types. The RE is therefore a composite element with one subregion essential for selecting the appropriate donor during switching, and a separate region involved in modulating chromosome conformation prior to switching.
2015-11-20 | GSE73890 | GEO
Project description:In this study, we report that glucose starvation and oxidative stress, common environmental stresses encountered by the pathogen, induce the development of mating projections and efficiently permit same-sex mating in C. albicans with an “a” mating type (MTLa/a).
2018-08-29 | GSE119165 | GEO