scholarly journals Properties of Gene Expression and Chromatin Structure with Mechanically Regulated Transcription

2018 ◽  
Author(s):  
Stuart A. Sevier ◽  
Herbert Levine
Keyword(s):  
Gene Expression ◽  
Mechanical Properties ◽  
Dna Structure ◽  
Genetic System ◽  
Dna Supercoiling ◽  
Simple Description ◽  
Gene Orientation ◽  
Physical Elements ◽  
Transcriptional Bursting ◽  
The Impact

The mechanical properties of transcription have emerged as central elements in our understanding of gene expression. Recent work has been done introducing a simple description of the basic physical elements of transcription where RNA elongation, RNA polymerase (RNAP) rotation and DNA supercoiling are coupled [1]. Here we generalize this framework to accommodate the behavior of many RNAPs operating on multiple genes on a shared piece of DNA. The resulting framework is combined with well-established stochastic processes of transcription resulting in a model which characterizes the impact of the mechanical properties of transcription on gene expression and DNA structure. Transcriptional bursting readily emerges as a common phenomenon with origins in the geometric nature of the genetic system and results in the bounding of gene expression statistics. Properties of a multiple gene system are examined with special attention paid to role that genome composition (gene orientation, size, and intergenic distance) plays in the ability of genes to transcribe. The role of transcription in shaping DNA structure is examined and the possibility of transcription driven domain formation is discussed.PACS numbers:

scholarly journals ModifyingSaccharomyces cerevisiaeAdhesion Properties Regulates Yeast Ecosystem Dynamics

mSphere ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Debra Rossouw ◽  
Skye P. Meiring ◽  
Florian F. Bauer
Keyword(s):  
Gene Expression ◽  
Gene Family ◽  
Yeast Species ◽  
Genetic System ◽  
Physical Contact ◽  
Relative Fitness ◽  
Independent Evidence ◽  
Content Type ◽  
Metabolic Interactions ◽  
The Impact

ABSTRACTPhysical contact between yeast species, in addition to better-understood and reported metabolic interactions, has recently been proposed to significantly impact the relative fitness of these species in cocultures. Such data have been generated by using membrane bioreactors, which physically separate two yeast species. However, doubts persist about the degree that the various membrane systems allow for continuous and complete metabolic contact, including the exchange of proteins. Here, we provide independent evidence for the importance of physical contact by using a genetic system to modify the degree of physical contact and, therefore, the degree of asexual intraspecies and interspecies adhesion in yeast. Such adhesion is controlled by a family of structurally related cell wall proteins encoded by theFLOgene family. As previously shown, the expression of specific members of theFLOgene family inSaccharomyces cerevisiaedramatically changes the coadhesion patterns between this yeast and other yeast species. Here, we use this differential aggregation mediated byFLOgenes as a model to assess the impact of physical contact between different yeast species on the relative fitness of these species in simplified ecosystems. The identity of theFLOgene has a marked effect on the persistence of specific non-Saccharomycesyeasts over the course of extended growth periods in batch cultures. Remarkably,FLO1andFLO5expression often result in opposite outcomes. The data provide clear evidence for the role of physical contact in multispecies yeast ecosystems and suggest thatFLOgene expression may be a major factor in such interactions.IMPORTANCEThe impact of direct (physical) versus indirect (metabolic) interactions between different yeast species has attracted significant research interest in recent years. This is due to the growing interest in the use of multispecies consortia in bioprocesses of industrial relevance and the relevance of interspecies interactions in establishing stable synthetic ecosystems. Compartment bioreactors have traditionally been used in this regard but suffer from numerous limitations. Here, we provide independent evidence for the importance of physical contact by using a genetic system, based on theFLOgene family, to modify the degree of physical contact and, therefore, the degree of asexual intraspecies and interspecies adhesion in yeast. Our results show that interspecies contact significantly impacts population dynamics and the survival of individual species. Remarkably, different members of theFLOgene family often lead to very different population outcomes, further suggesting thatFLOgene expression may be a major factor in such interactions.

scholarly journals Structural Coupling between RNA Polymerase Composition and DNA Supercoiling in Coordinating Transcription: a Global Role for the Omega Subunit?

mBio ◽  
2011 ◽  
Vol 2 (4) ◽  
Author(s):  
Marcel Geertz ◽  
Andrew Travers ◽  
Sanja Mehandziska ◽  
Patrick Sobetzko ◽  
Sarath Chandra Janga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Dna Supercoiling ◽  
Dna Topology ◽  
Chromosomal Dna ◽  
Tight Coupling ◽  
Structural Coupling ◽  
Bacterial Physiology ◽  
Transcription Machinery ◽  
The Impact

ABSTRACT In growing bacterial cells, the global reorganization of transcription is associated with alterations of RNA polymerase composition and the superhelical density of the DNA. However, the existence of any regulatory device coordinating these changes remains elusive. Here we show that in an exponentially growing Escherichia coli rpoZ mutant lacking the polymerase ω subunit, the impact of the Eσ38 holoenzyme on transcription is enhanced in parallel with overall DNA relaxation. Conversely, overproduction of σ70 in an rpoZ mutant increases both overall DNA supercoiling and the transcription of genes utilizing high negative superhelicity. We further show that transcription driven by the Eσ38 and Eσ70 holoenzymes from cognate promoters induces distinct superhelical densities of plasmid DNA in vivo. We thus demonstrate a tight coupling between polymerase holoenzyme composition and the supercoiling regimen of genomic transcription. Accordingly, we identify functional clusters of genes with distinct σ factor and supercoiling preferences arranging alternative transcription programs sustaining bacterial exponential growth. We propose that structural coupling between DNA topology and holoenzyme composition provides a basic regulatory device for coordinating genome-wide transcription during bacterial growth and adaptation. IMPORTANCE Understanding the mechanisms of coordinated gene expression is pivotal for developing knowledge-based approaches to manipulating bacterial physiology, which is a problem of central importance for applications of biotechnology and medicine. This study explores the relationships between variations in the composition of the transcription machinery and chromosomal DNA topology and suggests a tight interdependence of these two variables as the major coordinating principle of gene regulation. The proposed structural coupling between the transcription machinery and DNA topology has evolutionary implications and suggests a new methodology for studying concerted alterations of gene expression during normal and pathogenic growth both in bacteria and in higher organisms.

scholarly journals Collective polymerase dynamics emerge from DNA Supercoiling Mediated Transcription

2021 ◽  
Author(s):  
Stuart Sevier ◽  
Sahand Hormoz
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Dna Supercoiling ◽  
Toggle Switch ◽  
Endogenous Genes ◽  
Non Local ◽  
Physical Interactions ◽  
The Impact

All biological processes ultimately come from physical interactions. The mechanical properties of DNA play a critical role in transcription. RNA polymerase can over or under twist DNA (referred to as DNA supercoiling) when it moves along a gene resulting in mechanical stresses in DNA that impact its own motion and that of other polymerases. For example, when enough supercoiling accumulates, an isolated polymerase halts and transcription stops. DNA supercoiling can also mediate non-local interactions between polymerases that shape gene expression fluctuations. Here, we construct a comprehensive model of transcription that captures how RNA polymerase motion changes the degree of DNA supercoiling which in turn feeds back into the rate at which polymerases are recruited and move along the DNA. Surprisingly, our model predicts that a group of three or more polymerases move together at a constant velocity and sustain their motion (forming what we call a polymeton) whereas one or two polymerases would have halted. We further show that accounting for the impact of DNA supercoiling on both RNA polymerase recruitment and velocity recapitulates empirical observations of gene expression fluctuations. Finally, we propose a mechanical toggle switch whereby interactions between genes are mediated by DNA twisting as opposed to proteins. Understanding the mechanical regulation of gene expression provides new insights into how endogenous genes can interact and informs the design of new forms of engineered interactions.

Effect of combined drink cans and steel fibers on the impact resistance and mechanical properties of concrete

2020 ◽  
Vol 14 (2) ◽  
pp. 6734-6742
Author(s):  
A. Syamsir ◽  
S. M. Mubin ◽  
N. M. Nor ◽  
V. Anggraini ◽  
S. Nagappan ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Tensile Strength ◽  
Compressive Strength ◽  
Reinforced Concrete ◽  
Impact Resistance ◽  
Fiber Reinforced Concrete ◽  
Steel Fibers ◽  
Fiber Reinforced ◽  
Indirect Tensile ◽  
The Impact

This study investigated the combine effect of 0.2 % drink cans and steel fibers with volume fractions of 0%, 0.5%, 1%, 1.5%, 2%, 2.5% and 3% to the mechanical properties and impact resistance of concrete. Hooked-end steel fiber with 30 mm and 0.75 mm length and diameter, respectively was selected for this study.  The drinks cans fiber were twisted manually in order to increase friction between fiber and concrete. The results of the experiment showed that the combination of steel fibers and drink cans fibers improved the strength performance of concrete, especially the compressive strength, flexural strength and indirect tensile strength. The results of the experiment showed that the combination of steel fibers and drink cans fibers improved the compressive strength, flexural strength and indirect tensile strength by 2.3, 7, and 2 times as compare to batch 1, respectively. Moreover, the impact resistance of fiber reinforced concrete has increase by 7 times as compared to non-fiber concretes. Moreover, the impact resistance of fiber reinforced concrete consistently gave better results as compared to non-fiber concretes. The fiber reinforced concrete turned more ductile as the dosage of fibers was increased and ductility started to decrease slightly after optimum fiber dosage was reached. It was found that concrete with combination of 2% steel and 0.2% drink cans fibers showed the highest compressive, split tensile, flexural as well as impact strength.    

scholarly journals Aberrant expression of USF2 in refractory rheumatoid arthritis and its regulation of proinflammatory cytokines in Th17 cells

2020 ◽  
Vol 117 (48) ◽  
pp. 30639-30648
Author(s):  
Dan Hu ◽  
Emily C. Tjon ◽  
Karin M. Andersson ◽  
Gabriela M. Molica ◽  
Minh C. Pham ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
T Cells ◽  
Transcription Factor ◽  
Proinflammatory Cytokines ◽  
Th17 Cells ◽  
Gene Set Enrichment Analysis ◽  
Aberrant Expression ◽  
Signature Genes ◽  
The Impact

IL-17–producing Th17 cells are implicated in the pathogenesis of rheumatoid arthritis (RA) and TNF-α, a proinflammatory cytokine in the rheumatoid joint, facilitates Th17 differentiation. Anti-TNF therapy ameliorates disease in many patients with rheumatoid arthritis (RA). However, a significant proportion of patients do not respond to this therapy. The impact of anti-TNF therapy on Th17 responses in RA is not well understood. We conducted high-throughput gene expression analysis of Th17-enriched CCR6+CXCR3−CD45RA−CD4+T (CCR6+T) cells isolated from anti-TNF–treated RA patients classified as responders or nonresponders to therapy. CCR6+T cells from responders and nonresponders had distinct gene expression profiles. Proinflammatory signaling was elevated in the CCR6+T cells of nonresponders, and pathogenic Th17 signature genes were up-regulated in these cells. Gene set enrichment analysis on these signature genes identified transcription factor USF2 as their upstream regulator, which was also increased in nonresponders. Importantly, short hairpin RNA targetingUSF2in pathogenic Th17 cells led to reduced expression of proinflammatory cytokines IL-17A, IFN-γ, IL-22, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as transcription factor T-bet. Together, our results revealed inadequate suppression of Th17 responses by anti-TNF in nonresponders, and direct targeting of the USF2-signaling pathway may be a potential therapeutic approach in the anti-TNF refractory RA.

scholarly journals Pre-treatment clinical and gene expression patterns predict developmental change in early intervention in autism

2021 ◽  
Author(s):  
Michael V. Lombardo ◽  
Elena Maria Busuoli ◽  
Laura Schreibman ◽  
Aubyn C. Stahmer ◽  
Tiziano Pramparo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Treatment Outcome ◽  
Early Intervention ◽  
Developmental Change ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Time In Treatment ◽  
Pre Treatment ◽  
Blood Leukocyte ◽  
The Impact

AbstractEarly detection and intervention are believed to be key to facilitating better outcomes in children with autism, yet the impact of age at treatment start on the outcome is poorly understood. While clinical traits such as language ability have been shown to predict treatment outcome, whether or not and how information at the genomic level can predict treatment outcome is unknown. Leveraging a cohort of toddlers with autism who all received the same standardized intervention at a very young age and provided a blood sample, here we find that very early treatment engagement (i.e., <24 months) leads to greater gains while controlling for time in treatment. Pre-treatment clinical behavioral measures predict 21% of the variance in the rate of skill growth during early intervention. Pre-treatment blood leukocyte gene expression patterns also predict the rate of skill growth, accounting for 13% of the variance in treatment slopes. Results indicated that 295 genes can be prioritized as driving this effect. These treatment-relevant genes highly interact at the protein level, are enriched for differentially histone acetylated genes in autism postmortem cortical tissue, and are normatively highly expressed in a variety of subcortical and cortical areas important for social communication and language development. This work suggests that pre-treatment biological and clinical behavioral characteristics are important for predicting developmental change in the context of early intervention and that individualized pre-treatment biology related to histone acetylation may be key.

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