Scaling of cellular gene expression with ploidy
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PROVIDER: PRJNA682117 | ENA |
REPOSITORIES: ENA
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Project description:Whereas most eukaryotic cells are diploid, carrying two chromosome sets, variances in ploidy are common. Despite the relative prevalence of ploidy changes and their relevance for pathology and evolution, the consequences of altered ploidy for cellular gene expression remain poorly understood. We quantified changes in the transcriptome and proteome of the yeast Saccharomyces cerevisiae with different ploidy, from the haploid to the tetraploid state. We found that the abundance of proteins increases with ploidy, but does not scale proportionally with increasing DNA content, suggesting a compensatory, cellular response to increases in ploidy. We further found that pathways related to cytoplasmic ribosomes and translation are differentially regulated. With increasing ploidy the cells reduced the rRNA and ribosomal protein abundance, although they maintained a constant translational output. These adaptations stem from an active process that involves the kinases Tor1 and Sch9 and the transcriptional corepressor of rDNA transcription, Tup1. Consistent with our results in yeast, human tetraploid cells show reduced mTORC1 activity and downregulated their ribosome content via the Tup1 homolog Tle1, demonstrating that the proteome remodeling pathway discovered here constitutes a conserved response pathway to increased ploidy.
2022-08-15 | GSE162513 | GEO
Project description:While most eukaryotic cells are diploid, with two chromosome sets, variances in ploidy are common. Despite the relative prevalence of ploidy changes and their relevance for pathology and evolution, a complete picture of consequences of altered ploidy is missing. We analyzed transcriptome and proteome changes in budding yeast Saccharomyces cerevisiae from haploid to tetraploid and found that the mRNA and protein abundance increases linearly with ploidy, but does not double with doubling the DNA content. Besides this linear increase, we found that pathways related to mitochondria and to cytoplasmic ribosomes and translation are differentially regulated. Indeed, with increasing ploidy the cells reduce mitochondrial content and this effect can be rescued by antioxidants. Moreover, cells of higher ploidy reduce their ribosome content while maintaining constant translational output. We show that this is an active process regulated via the Tor1 and Sch9 kinases and a transcriptional corepressor of rDNA transcription, Tup1. Similarly, human tetraploid cells downregulate their ribosome content via Tle1, a Tup1 homolog, demonstrating that the proteome remodeling is a conserved response to increased ploidy.
2022-08-15 | PXD022605 | Pride
Project description:We investigated the effects of the ploidy on cellular response in strains carrying various types of gross chromosomal rearrangements.
2011-06-17 | GSE28285 | GEO
Project description:Synaptic scaling is a form of homeostatic plasticity which allows neurons to reduce their action potential firing rate in response to chronic alterations in neural activity. Synaptic scaling requires profound changes in gene expression, but the relative contribution of local and cell-wide mechanisms to synaptic scaling is controversial. Here we performed a comprehensive multi-omics characterization of the somatic and process compartments of primary rat hippocampal neurons during synaptic scaling. Thereby, we uncovered highly compartment-specific and correlated changes in the neuronal transcriptome and proteome. Specifically, we identified highly compartment-specific downregulation of crucial regulators of neuronal excitability and excitatory synapse structure. Motif analysis further suggests an important role for trans-acting post-transcriptional regulators, including RNA-binding proteins and microRNAs, in the local regulation of the corresponding mRNAs. Altogether, our study indicates that compartmentalized gene expression changes are widespread in synaptic scaling and might co-exist with neuron-wide mechanism to allow synaptic computation and homeostasis.
2021-07-06 | GSE155540 | GEO
Project description:Scaling of gene expression with liver cell size in vivo
| PRJEB3304 | ENA
Project description:Compartment-specific regulation of gene expression orchestrates homeostatic synaptic scaling
| PRJNA650210 | ENA
Project description:Ploidy changes are frequent in nature and contribute to evolution, functional specialization and tumorigenesis. Analysis of model organisms of different ploidies revealed that increased ploidy leads to an increase in cell and nuclear volume, reduced proliferation, metabolic changes, lower fitness, and increased genomic instability, but the underlying mechanisms remain poorly understood. To investigate how gene expression changes with cellular ploidy, we analyzed isogenic series of budding yeasts from 1N to 4N. We show that mRNA and protein abundance scales allometrically with ploidy, with tetraploid cells showing only threefold increase in protein abundance compared to haploids. This ploidy-dependent sublinear scaling occurs via decreased rRNA and ribosomal protein abundance and reduced translation. We demonstrate that the activity of Tor1 is reduced with increasing ploidy, which leads to diminished rRNA gene repression via a Tor1-Sch9-Tup1 signaling pathway. mTORC1 and S6K activity are also reduced in human tetraploid cells and the concomitant increase of the Tup1 homolog Tle1 downregulates the rDNA transcription. Our results suggest that the mTORC1-Sch9/S6K-Tup1/TLE1 pathway ensures proteome remodeling in response to increased ploidy.
| S-EPMC9581932 | biostudies-literature
Project description:We investigated the effects of the ploidy on cellular response in strains carrying various types of gross chromosomal rearrangements. Fourteen mutated strains (6 haploid strains and 8 diploid strains) were compared to their associated parental strain (haploid or diploid parental strain). For each comparison, 2 microarray experiments implying biological replicates were performed.
2011-06-17 | E-GEOD-28285 | biostudies-arrayexpress
Project description:Heterosis and polyploidy are two important aspects of plant evolution. To examine these issues, we conducted a global gene expression study of a maize ploidy series as well as a set of tetraploid inbred and hybrid lines. This gene expression analysis complements an earlier phenotypic study of these same materials. We find that ploidy change affects a large fraction of the genome, albeit at low levels; gene expression changes rarely exceed 2-fold and are typically not statistically significant. The most common gene expression profile we detected is greater than linear increase from monoploid to diploid, and reductions from diploid to triploid and from triploid to tetraploid, a trend that mirrors plant stature. When examining heterosis in tetraploid maize lines, we found a large fraction of the genome impacted but the majority of changes were not statistically significant at 2-fold or less. Non-additive expression was common in the hybrids, and the extent of non-additivity increased both in number and magnitude from duplex to quadruplex hybrids. Overall, we find that gene expression trends mirror observations from the phenotypic studies; however, obvious mechanistic connections remain unknown.
2010-11-30 | GSE25526 | GEO
Project description:Evidence suggests that increases in ploidy have occurred frequently in the evolutionary history of organisms, and can serve adaptive functions to specialized, somatic cells in multicellular organisms (Edgar & Orr-Weaver, 2001; Orr-Weaver, 2015; Van De Peer et al., 2017). However, the sudden multiplication of all chromosome content may present physiological challenges to the cells in which it occurs. Experimental studies have associated increases in ploidy with reduced cell survival and proliferation (Andalis et al., 2004; Fujiwara et al., 2005). To understand the physiological challenges that suddenly-increased chromosome content imposes on cells, we used S. cerevisiae cells to ask how much chromosomal DNA cells may contain, and what determines this limit. We generated polyploid cells using two distinct methods causing cells to undergo endoreplication and identified the maximum ploidy of these cells, 32-64C. We found that physical determinants that alleviate or exacerbate cell surface stress increase and decrease the limit to ploidy, respectively. We also used these cells to investigate gene expression changes associated with increased ploidy, and identified the repression of genes involved in ergosterol biosynthesis. We propose that ploidy is inherently limited by the impacts of growth in size, which accompany whole genome duplication, to cell surface integrity.
2024-12-03 | GSE275298 | GEO