Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional and chromatin-based partitioning mechanisms uncouple protein scaling from cell size

ABSTRACT: Biosynthesis scales with cell size such that protein concentrations generally remain constant as cells grow. As an exception, synthesis of the cell-cycle inhibitor Whi5 ‘sub-scales’ with cell size so that its concentration is lower in larger cells to promote cell-cycle entry. Here, we find that a transcriptional control uncouples Whi5 synthesis from cell size and, screening for similar genes, identify histones as the major class of sub-scaling transcripts besides WHI5. Histone synthesis is thereby matched to genome content rather than cell size. Such sub-scaling proteins are challenged by asymmetric cell division because proteins are typically partitioned in proportion to new-born cell volume. To avoid this fate, Whi5 uses chromatin-binding to partition similar protein amounts to each new-born cell regardless of cell size. Finally, disrupting both Whi5 synthesis and chromatin-based partitioning compromises G1 size control. Thus, specific transcriptional and partitioning mechanisms determine protein sub-scaling to control cell size.

ORGANISM(S): Saccharomyces cerevisiae Schizosaccharomyces pombe

PROVIDER: GSE167842 | GEO | 2021/12/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcriptional and chromatin-based partitioning mechanisms uncouple protein scaling from cell size

Project description:Transcriptional and chromatin-based partitioning mechanisms uncouple protein scaling from cell size

| PRJNA705222 | ENA

Differential scaling of gene expression with cell size may explain size control in budding yeast.

Project description:Yeast cells must grow to a critical size before committing to division. It is unknown how size is measured. We find that as cells grow, mRNAs for some cell cycle activators scale faster than size, increasing in concentration, while mRNAs for some inhibitors scale slower than size, decreasing in concentration. Size-scaled gene expression could cause an increasing ratio of activators to inhibitors with size, triggering cell cycle entry. Consistent with this, expression of the CLN2 activator from the promoter of the WHI5 inhibitor, or vice versa, interfered with cell size homeostasis, yielding a broader distribution of cell sizes. We suggest that size homeostasis comes from differential scaling of gene expression with size. Such regulation of gene expression as a function of cell size could affect many cellular processes.

2020-02-16 | GSE145206 | GEO

IGF1 treatment of developing mouse molar

Project description:When evolution leads to differences in body size, organs generally scale along. A well-known example of the tight relationship between organ and body size is the scaling of mammalian molar teeth. To investigate how teeth scale during development and evolution, we compared mouse and rat molar development from initiation through final size. Whereas the linear dimensions of the rat first lower molar are twice that of the mouse molar, their shapes are largely the same. We found that scaling of the molars starts early, and that the rat molar is patterned equally as fast but in a larger size than the mouse molar. Using transcriptomics, we discovered that a known regulator of body size, insulin-like growth factor 1 (Igf1), is more highly expressed in the rat molars compared to the mouse molars. Ex vivo and in vivo mouse models demonstrated that modulation of the IGF pathway reproduces several aspects of the observed scaling process. Furthermore, analysis of IGF1-treated mouse molars and computational modeling indicate that IGF signalling scales teeth by simultaneously inhibiting the cusp patterning programme and by enhancing growth, thereby providing a relatively simple mechanism for scaling teeth during development and evolution. Finally, comparative data from shrews to elephants suggest that this scaling of patterning mechanism regulates the minimum tooth size possible, as well as the patterning potential of large teeth.

2022-11-19 | GSE218338 | GEO

Differential scaling between G1 protein production and cell size dynamics promotes commitment to the cell division cycle in budding yeast

Project description:In the unicellular eukaryote Saccharomyces cerevisiae, Cln3–cyclin-dependent kinase activity enables Start, the irreversible commitment to the cell division cycle. However, the concentration of Cln3 has been paradoxically considered to remain constant during G1, due to the presumed scaling of its production rate with cell size dynamics. Measuring metabolic and biosynthetic activity during cell cycle progression in single cells, we found that cells exhibit pulses in their protein production rate. Rather than scaling with cell size dynamics, these pulses follow the intrinsic metabolic dynamics, peaking around Start. Using a viral- based bicistronic construct and targeted proteomics to measure Cln3 at the single-cell and population levels, we show that the differential scaling between protein production and cell size leads to a temporal increase in Cln3 concentration, and passage through Start. This differential scaling causes Start in both daughter and mother cells across growth conditions. Thus, uncou- pling between two fundamental physiological parameters drives cell cycle commitment.

2022-05-16 | PXD029959 | Pride

Scaling of gene expression with liver cell size in vivo

Project description:Scaling of gene expression with liver cell size in vivo

| PRJEB3304 | ENA

Differential scaling of gene expression with cell size may explain size control in budding yeast.

Project description:Differential scaling of gene expression with cell size may explain size control in budding yeast.

| PRJNA606307 | ENA

RNA polymerase II dynamics and mRNA stability feedback scale mRNA amounts with cell size

Project description:A fundamental feature of cellular growth is that total protein and RNA amounts increase with cell size to keep concentrations approximately constant. A key component to this is that global transcription rates increase in larger cells. Here, we identify RNAPII as the limiting factor scaling mRNA transcription with cell size in budding yeast, as transcription is highly sensitive to the dosage of RNAPII but not to other components of the transcriptional machinery. Our experiments support a dynamic equilibrium model where global RNAPII transcription at a given size is set by the mass-action recruitment kinetics of unengaged nucleoplasmic RNAPII to the genome. However, this only drives a sub-linear increase in transcription with size, which is then partially compensated for by a decrease in mRNA decay rates as cells enlarge. Thus, limiting RNAPII and feedback on mRNA stability work in concert to scale mRNA amounts with cell size.

2023-11-01 | GSE242874 | GEO

Differential scaling between G1 protein production and cell size dynamics promotes commitment to the cell division cycle in budding yeast

Project description:In the unicellular eukaryote Saccharomyces cerevisiae, Cln3-CDK activity enables Start, the irreversible commitment to the cell division cycle. However, the concentration of Cln3 has been paradoxically considered to remain constant during G1, due to the presumed scaling of its production rate with cell size dynamics. Measuring metabolic and biosynthetic activity during cell cycle progression in single cells, we found that cells exhibit pulses in protein production rate, which do not scale with cell size dynamics, but -following the intrinsic metabolic dynamics- peak around Start. Using a viral-based bicistronic construct and targeted proteomics to measure Cln3 at the single-cell and population level, we show that the differential scaling between protein production and cell size leads to a temporal increase in Cln3 concentration, and passage through Start. This differential scaling causes Start in both daughter and mother cells, across growth conditions. Thus, uncoupling between two fundamental physiological parameters drives cell cycle commitment.

2019-10-29 | PXD015327 | Pride

Role of a Candida albicans Whi5/Nrm1 homolog in cell cycle and hyphal-specific gene expression

Project description:Candida albicans is an opportunistic pathogenic fungus that is able to assume several morphologies, including yeast and hyphal growth forms. The hyphal morphology can be induced by various environmental stimuli and is accompanied by expression of a large set of hyphal-specific genes (HSGs). Cell cycle and morphogenetic programs are interconnected: notably, inhibition of cell cycle progression often causes a switch to filamentous growth. Here we identify and characterize CaNrm1, a C. albicans homolog of the S. cerevisiae Whi5 and Nrm1 transcription inhibitors that, analogous to mammalian Rb, regulate the cell cycle transcription program in the G1 phase and at the G1/S transition. CaNRM1 is able to complement the phenotypes of both whi5 and nrm1 mutants in S. cerevisiae. Deletion of CaNRM1 causes a reduction in cell size and results in increased resistance to hydroxyurea (HU), an inhibitor of DNA replication; analysis of the expression of ribonucleotide reductase, the target of HU, suggests that its transcriptional induction in response to HU is mainly dependent upon CaNrm1. Genetic epistasis analysis suggests that CaNrm1 interacts with the SBF and MBF transcription factors in S. cerevisiae and with the MBF functional homolog in C. albicans. At the transcription level, deletion of CaNRM1 causes an induction of many G1 and G1/S-specific genes. Induction of the HSGs is dampened under certain conditions in the Canrm1-/- mutant, suggesting that the cell cycle transcription program influences the morphogenetic transcription program of C. albicans. One aspect of the characterization of the C. albicans Whi5/Nrm1 gene was to examine how this molecule influences global gene expression. To that end, we isolated total RNA from log-phase nrm1-/nrm1- (as well as parent/background strain) cells in two independent replicate experiments. These samples were processed, labeled, and subsequently used for hybridization of custom C. albicans Affymetrix arrays.

2012-01-01 | E-GEOD-20612 | biostudies-arrayexpress

Budding yeast size control by titration of nuclear sites

Project description:This model is decribed in the article: Dilution and titration of cell-cycle regulators may control cell size in budding yeast Frank S. Heldt, Reece Lunstone, John J. Tyson, Bela Novak PLoS Comput Biol, October 2018, 14(10), e1006548, doi: 10.1371/journal.pcbi.1006548 Abstract: The size of a cell sets the scale for all biochemical processes within it, thereby affecting cellular fitness and survival. Hence, cell size needs to be kept within certain limits and relatively constant over multiple generations. However, how cells measure their size and use this information to regulate growth and division remains controversial. Here, we present two mechanistic mathematical models of the budding yeast (S. cerevisiae) cell cycle to investigate competing hypotheses on size control: inhibitor dilution and titration of nuclear sites. Our results suggest that an inhibitor-dilution mechanism, in which cell growth dilutes the transcriptional inhibitor Whi5 against the constant activator Cln3, can facilitate size homeostasis. This is achieved by utilising a positive feedback loop to establish a fixed size threshold for the START transition, which efficiently couples cell growth to cell cycle progression. Yet, we show that inhibitor dilution cannot reproduce the size of mutants that alter the cell’s overall ploidy and WHI5 gene copy number. By contrast, size control through titration of Cln3 against a constant number of genomic binding sites for the transcription factor SBF recapitulates both size homeostasis and the size of these mutant strains. Moreover, this model produces an imperfect ‘sizer’ behaviour in G1 and a ‘timer’ in S/G2/M, which combine to yield an ‘adder’ over the whole cell cycle; an observation recently made in experiments. Hence, our model connects these phenomenological data with the molecular details of the cell cycle, providing a systems-level perspective of budding yeast size control.

2019-11-13 | BIOMD0000000856 | BioModels

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data