scholarly journals Gene transcription as a limiting factor in protein production and cell growth

2019 ◽  
Author(s):  
Eyal Metzl-Raz ◽  
Moshe Kafri ◽  
Gilad Yaakov ◽  
Naama Barkai
Keyword(s):  
Gene Expression ◽  
Growth Rate ◽  
Cell Growth ◽  
Cell Size ◽  
Protein Production ◽  
Transcript Abundance ◽  
Limiting Factor ◽  
Gene Promoters ◽  
Proliferating Cells ◽  
Endogenous Gene

AbstractGrowth rate and cell size are principle characteristics of proliferating cells, whose values depend on cellular biosynthetic processes in a way poorly understood. Protein production is critical for growth, and we therefore examined for processes limiting this production. Burdening cells with an excess of inert protein changed endogenous gene expression similarly to transcription-perturbing mutants, was epistatic to these mutants, but did not deplete respective factors from gene promoters. Mathematical modeling, corroborated by experiments, attributed this signature to a feedback which proportionally increases all endogenous gene expression, but lags at fast initiating genes already transcribed close to the maximal possible rate. As a possible benefit of maximizing transcription rates, we discuss a conflict between cell growth rate and size, which emerges above a critical cell size set by transcript abundance. We propose that biochemical limits on protein and mRNA production define the characteristic values of cell size and division time.

scholarly journals Non-invasive somatotransgenic bioimaging in living animals

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1216 ◽  
Author(s):  
Juliette M. Delhove ◽  
Rajvinder Karda ◽  
Lorna M. FitzPatrick ◽  
Suzanne M.K. Buckley ◽  
Simon N. Waddington ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reporter Gene ◽  
Viral Vectors ◽  
Es Cells ◽  
Embryonic Stem ◽  
Whole Body ◽  
Luciferase Reporter ◽  
Gene Promoters ◽  
Luciferase Reporter Gene ◽  
Endogenous Gene

Bioluminescence imaging enables noninvasive quantification of luciferase reporter gene expression in transgenic tissues of living rodents. Luciferase transgene expression can be regulated by endogenous gene promoters after targeted knock-in of the reporter gene, usually within the first intron of the gene. Even using CRISPR/Cas9 mediated genome editing this can be a time consuming and costly process. The generation of germline transgenic (GLT) rodents by targeted genomic integration of a gene expression cassette in embryonic stem (ES) cells is commonplace but results in the wastage of large numbers of animals during colony generation, back-crossing and maintenance. Using a synthetic/truncated promoter-driven luciferase gene to study promoter activity in a given tissue or organ of a GLT also often results in unwanted background luciferase activity during whole-body bioluminescent imaging as every cell contains the reporter. We have developed somatotransgenic bioimaging; a method to generate tissue-restricted transcription factor activated luciferase reporter (TFAR) cassettes in rodents that substantially reduces the number of animals required for experimentation. Bespoke designed TFARs are delivered to newborn pups using viral vectors targeted to specific organs by tissue-tropic pseudotypes. Retention and proliferation of TFARs is facilitated by stem/progenitor cell transduction and immune tolerance to luciferase due to the naïve neonatal immune system. We have successfully applied both lentiviral and adeno-associated virus (AAV) vectors in longitudinal rodent studies, targeting TFARs to the liver and brain during normal development and in well-established disease models. Development of somatotransgenic animals has broad applicability to non-invasively determine mechanistic insights into homeostatic and disease states and assess toxicology and efficacy testing. Somatotransgenic bioimaging technology is superior to current whole-body, light-emitting transgenic models as it reduces the numbers of animals used by generating only the required number of animals. It is also a refinement over current technologies given the ability to use conscious, unrestrained animals.

scholarly journals The Tor Pathway Regulates Gene Expression by Linking Nutrient Sensing to Histone Acetylation

2003 ◽  
Vol 23 (2) ◽  
pp. 629-635 ◽  
Author(s):  
John R. Rohde ◽  
Maria E. Cardenas
Keyword(s):  
Gene Expression ◽  
Cell Growth ◽  
Histone Acetylation ◽  
Nutrient Sensing ◽  
Gene Promoters ◽  
Histone H4 ◽  
Tor Pathway ◽  
Histone H4 Acetylation ◽  
Promoter Occupancy ◽  
Histone H4 Deacetylation

ABSTRACT The Tor pathway mediates cell growth in response to nutrient availability, in part by inducing ribosomal protein (RP) gene expression via an unknown mechanism. Expression of RP genes coincides with recruitment of the Esa1 histone acetylase to RP gene promoters. We show that inhibition of Tor with rapamycin releases Esa1 from RP gene promoters and leads to histone H4 deacetylation without affecting promoter occupancy by Rap1 and Abf1. Genetic and biochemical evidence identifies Rpd3 as the major histone deacetylase responsible for reversing histone H4 acetylation at RP gene promoters in response to Tor inhibition by rapamycin or nutrient limitation. Our results illustrate that the Tor pathway links nutrient sensing with histone acetylation to control RP gene expression and cell growth.

scholarly journals Variation in the expression of a transmembrane protein influences cell growth in Arabidopsis thaliana petals by altering auxin responses

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Charlotte N. Miller ◽  
Jack Dumenil ◽  
Fu Hao Lu ◽  
Caroline Smith ◽  
Neil McKenzie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Arabidopsis Thaliana ◽  
Genetic Variation ◽  
Cell Growth ◽  
Plant Growth ◽  
Cell Size ◽  
Natural Populations ◽  
Organ Size ◽  
Substantial Contribution ◽  
Over Expression

Abstract Background The same species of plant can exhibit very diverse sizes and shapes of organs that are genetically determined. Characterising genetic variation underlying this morphological diversity is an important objective in evolutionary studies and it also helps identify the functions of genes influencing plant growth and development. Extensive screens of mutagenised Arabidopsis populations have identified multiple genes and mechanisms affecting organ size and shape, but relatively few studies have exploited the rich diversity of natural populations to identify genes involved in growth control. Results We screened a relatively well characterised collection of Arabidopsis thaliana accessions for variation in petal size. Association analyses identified sequence and gene expression variation on chromosome 4 that made a substantial contribution to differences in petal area. Variation in the expression of a previously uncharacterised gene At4g16850 (named as KSK) had a substantial role on variation in organ size by influencing cell size. Over-expression of KSK led to larger petals with larger cells and promoted the formation of stamenoid features. The expression of auxin-responsive genes known to limit cell growth was reduced in response to KSK over-expression. ANT expression was also reduced in KSK over-expression lines, consistent with altered floral identities. Auxin responses were reduced in KSK over-expressing cells, consistent with changes in auxin-responsive gene expression. KSK may therefore influence auxin responses during petal development. Conclusions Understanding how genetic variation influences plant growth is important for both evolutionary and mechanistic studies. We used natural populations of Arabidopsis thaliana to identify sequence variation in a promoter region of Arabidopsis accessions that mediated differences in the expression of a previously uncharacterised membrane protein. This variation contributed to altered auxin responses and cell size during petal growth.

A β1-adrenergic receptor CaM kinase II-dependent pathway mediates cardiac myocyte fetal gene induction

2006 ◽  
Vol 291 (3) ◽  
pp. H1299-H1308 ◽  
Author(s):  
Carmen C. Sucharov ◽  
Peter D. Mariner ◽  
Karin R. Nunley ◽  
Carlin Long ◽  
Leslie Leinwand ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Cardiac Myocyte ◽  
Ventricular Myocytes ◽  
Gene Induction ◽  
Neonatal Rat ◽  
Gene Promoters ◽  
Endogenous Gene ◽  
Neonatal Rat Cardiac Myocytes ◽  
Neonate Rat

β-Adrenergic signaling plays an important role in the natural history of dilated cardiomyopathies. Chronic activation of β-adrenergic receptors (β1-AR and β2-AR) during periods of cardiac stress ultimately harms the failing heart by mechanisms that include alterations in gene expression. Here, we show that stimulation of β-ARs with isoproterenol in neonate rat ventricular myocytes causes a “fetal” response in the relative activities of the human cardiac fetal and/or adult gene promoters that includes repression of the human and rat α-myosin heavy chain (α-MyHC) promoters with simultaneous activation of the human atrial natriuretic peptide (ANP) and rat β-MyHC promoters. We also show that the promoter changes correlate with changes in endogenous gene expression as measured by mRNA expression. Furthermore, we show that these changes are specifically mediated by the β1-AR, but not the β2-AR, and are independent of α1-AR stimulation. We also demonstrate that the fetal gene response is independent of cAMP and protein kinase A, whereas inhibition of Ca2+/calmodulin-dependent protein kinase (CaMK) pathway blocks isoproterenol-mediated fetal gene program induction. Finally, we show that induction of the fetal program is dependent on activation of the L-type Ca2+ channel. We conclude that in neonatal rat cardiac myocytes, agonist-occupied β1-AR mobilizes Ca2+ stores to activate fetal gene induction through cAMP independent pathways that involve CaMK.

scholarly journals Variation in the expression of a transmembrane protein influences cell growth in Arabidopsis thaliana petals by altering auxin responses.

2020 ◽  
Author(s):  
Charlotte N. Miller ◽  
Jack Dumenil ◽  
Fu Hao Lu ◽  
Caroline Smith ◽  
Neil McKenzie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Arabidopsis Thaliana ◽  
Genetic Variation ◽  
Cell Growth ◽  
Plant Growth ◽  
Cell Size ◽  
Natural Populations ◽  
Organ Size ◽  
Substantial Contribution ◽  
Over Expression

Abstract Background The same species of plant can exhibit highly diverse sizes and shapes of organs that are genetically determined. Characterising genetic variation underlying this morphological diversity is an important objective in evolutionary studies and it also helps identify the functions of genes influencing plant growth and development. Extensive screens of mutagenised Arabidopsis populations have identified multiple genes and mechanisms affecting organ size and shape, but relatively few studies have exploited the rich diversity of natural populations to identify genes involved in growth control. Results We screened a relatively well characterised collection of Arabidopsis thaliana ecotypes for variation in petal size. Association analyses identified sequence and gene expression variation on chromosome 4 that made a substantial contribution to differences in petal area. Variation in the expression of a previously uncharacterised gene At4g16850 (named as KSK ) had a substantial role on variation in organ size by influencing cell size. Over-expression of KSK led to larger petals with larger cells and promoted the formation of stamenoid features. The expression of auxin-responsive genes known to limit cell growth was reduced in response to KSK over-expression. ANT expression was also reduced in KSK over-expression lines, consistent with altered floral identities. Auxin responses were reduced in KSK over-expressing cells, consistent with changes in auxin-responsive gene expression. KSK may therefore influence auxin availability during petal development. Conclusions Understanding how genetic variation influences plant growth is important for both evolutionary and mechanistic studies. We used natural populations of Arabidopsis thaliana to identify sequence variation in a promoter region of Arabidopsis ecotypes that mediated differences in the expression of a previously undescribed membrane protein. This variation contributed to altered auxin availability and cell size during petal growth.

scholarly journals Steady-state and dynamic gene expression programs inSaccharomyces cerevisiaein response to variation in environmental nitrogen

2016 ◽  
Vol 27 (8) ◽  
pp. 1383-1396 ◽  
Author(s):  
Edoardo M. Airoldi ◽  
Darach Miller ◽  
Rodoniki Athanasiadou ◽  
Nathan Brandt ◽  
Farah Abdul-Rahman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Rate ◽  
Steady State ◽  
Cell Growth ◽  
Nitrogen Source ◽  
Transcriptional Control ◽  
Molecular Form ◽  
Protein Translation ◽  
Cell Growth Rate ◽  
Regulated Gene Expression

Cell growth rate is regulated in response to the abundance and molecular form of essential nutrients. In Saccharomyces cerevisiae (budding yeast), the molecular form of environmental nitrogen is a major determinant of cell growth rate, supporting growth rates that vary at least threefold. Transcriptional control of nitrogen use is mediated in large part by nitrogen catabolite repression (NCR), which results in the repression of specific transcripts in the presence of a preferred nitrogen source that supports a fast growth rate, such as glutamine, that are otherwise expressed in the presence of a nonpreferred nitrogen source, such as proline, which supports a slower growth rate. Differential expression of the NCR regulon and additional nitrogen-responsive genes results in >500 transcripts that are differentially expressed in cells growing in the presence of different nitrogen sources in batch cultures. Here we find that in growth rate–controlled cultures using nitrogen-limited chemostats, gene expression programs are strikingly similar regardless of nitrogen source. NCR expression is derepressed in all nitrogen-limiting chemostat conditions regardless of nitrogen source, and in these conditions, only 34 transcripts exhibit nitrogen source–specific differential gene expression. Addition of either the preferred nitrogen source, glutamine, or the nonpreferred nitrogen source, proline, to cells growing in nitrogen-limited chemostats results in rapid, dose-dependent repression of the NCR regulon. Using a novel means of computational normalization to compare global gene expression programs in steady-state and dynamic conditions, we find evidence that the addition of nitrogen to nitrogen-limited cells results in the transient overproduction of transcripts required for protein translation. Simultaneously, we find that that accelerated mRNA degradation underlies the rapid clearing of a subset of transcripts, which is most pronounced for the highly expressed NCR-regulated permease genes GAP1, MEP2, DAL5, PUT4, and DIP5. Our results reveal novel aspects of nitrogen-regulated gene expression and highlight the need for a quantitative approach to study how the cell coordinates protein translation and nitrogen assimilation to optimize cell growth in different environments.

NM23 gene expression correlates with cell growth rate and S-phase

1995 ◽  
Vol 60 (6) ◽  
pp. 837-842 ◽  
Author(s):  
Maria A. Caligo ◽  
Giovanna Cipollini ◽  
Lisa Fiore ◽  
Simonetta Calvo ◽  
Fulvio Basolo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Rate ◽  
Cell Growth ◽  
S Phase ◽  
Cell Growth Rate ◽  
Nm23 Gene

scholarly journals Variation in the expression of a transmembrane protein influences cell growth in Arabidopsis thaliana petals by altering auxin availability

2020 ◽  
Author(s):  
Charlotte N. Miller ◽  
Jack Dumenil ◽  
Caroline Smith ◽  
Fu Hao Lu ◽  
Neil McKenzie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Arabidopsis Thaliana ◽  
Genetic Variation ◽  
Cell Growth ◽  
Plant Growth ◽  
Cell Size ◽  
Natural Populations ◽  
Organ Size ◽  
Substantial Contribution ◽  
Over Expression

AbstractBackgroundThe same species of plant can exhibit highly diverse sizes and shapes of organs that are genetically determined. Defining genetic variation underlying this morphological diversity is an important objective in evolutionary studies and it also helps identify the functions of genes influencing plant growth and development. Extensive screens of mutagenised Arabidopsis populations have identified multiple genes and mechanisms affecting organ size and shape, but relatively few studies have exploited the rich diversity of natural populations to identify genes involved in growth control.ResultsWe screened a relatively well characterised collection of Arabidopsis thaliana ecotypes for variation in petal size. Association analyses identified sequence and gene expression variation on chromosome 4 that made a substantial contribution to differences in petal area. Variation in expression of At4g16850 (named as KSK), encoding a hypothetical protein, had a substantial role on variation in organ size by influencing cell size. Over-expression of KSK led to larger petals with larger cells and promoted the formation of stamenoid features. The expression of auxin-responsive genes known to limit cell growth was reduced in response to KSK over-expression. ANT expression was also reduced in KSK over-expression lines, consistent with altered floral identities. Auxin availability was reduced in KSK over-expressing cells, consistent with changes in auxin-responsive gene expression. KSK may therefore influence auxin availability during petal development.ConclusionsUnderstanding how genetic variation influences plant growth is important for both evolutionary and mechanistic studies. We used natural populations of Arabidopsis thaliana to identify sequence variation in a promoter region of Arabidopsis ecotypes that mediated differences in the expression of a previously uncharacterised membrane protein. This variation contributed to altered auxin availability and cell size during petal growth.

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