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Stochastic gene regulation

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https://www.readbyqxmd.com/read/28427910/stochasticity-of-gene-expression-as-a-motor-of-epigenetics-in-bacteria-from-individual-to-collective-behavior
#1
REVIEW
Stéphanie Bury-Moné, Bianca Sclavi
Measuring gene expression at the single cell and single molecule level has recently made possible the quantitative measurement of stochasticity of gene expression. This enables identification of the probable sources and roles of noise. Stochastic gene expression can result in bacterial population heterogeneity, offering specific advantages for fitness and survival in various environments. This trait is therefore selected during the evolution of the species, and is consequently regulated by specific genetic network architecture...
April 18, 2017: Research in Microbiology
https://www.readbyqxmd.com/read/28414750/effect-of-transcription-factor-resource-sharing-on-gene-expression-noise
#2
Dipjyoti Das, Supravat Dey, Robert C Brewster, Sandeep Choubey
Gene expression is intrinsically a stochastic (noisy) process with important implications for cellular functions. Deciphering the underlying mechanisms of gene expression noise remains one of the key challenges of regulatory biology. Theoretical models of transcription often incorporate the kinetics of how transcription factors (TFs) interact with a single promoter to impact gene expression noise. However, inside single cells multiple identical gene copies as well as additional binding sites can compete for a limiting pool of TFs...
April 17, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28402875/tracking-low-copy-transcription-factors-in-living-bacteria-the-case-of-the-lac-repressor
#3
Federico Garza de Leon, Laura Sellars, Mathew Stracy, Stephen J W Busby, Achillefs N Kapanidis
Transcription factors control the expression of genes by binding to specific sites in DNA and repressing or activating transcription in response to stimuli. The lac repressor (LacI) is a well characterized transcription factor that regulates the ability of bacterial cells to uptake and metabolize lactose. Here, we study the intracellular mobility and spatial distribution of LacI in live bacteria using photoactivated localization microscopy combined with single-particle tracking. Since we track single LacI molecules in live cells by stochastically photoactivating and observing fluorescent proteins individually, there are no limitations on the copy number of the protein under study; as a result, we were able to study the behavior of LacI in bacterial strains containing the natural copy numbers (∼40 monomers), as well as in strains with much higher copy numbers due to LacI overexpression...
April 11, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28391018/macronuclear-actin-copy-number-variations-in-single-cells-of-different-pseudokeronopsis-alveolata-ciliophora-populations
#4
Lijuan Huang, Xuefen Lu, Changyu Zhu, Xiaofeng Lin, Zhenzhen Yi
Macronuclear chromosomes of ciliates, especially those of Spirotrichea, Armophorea and Phyllopharyngea, are extensively fragmented and their copy numbers vary significantly. A recent study suggested that parental RNA molecules regulate macronuclear copy number in offspring cells after conjugation. However, variations in patterns of macronuclear copy number during vegetative growth are not clear. Previous studies have reported macronuclear copy numbers of population averages, potentially masking individual variation...
March 3, 2017: European Journal of Protistology
https://www.readbyqxmd.com/read/28386100/petri-net-computational-modelling-of-langerhans-cell-interferon-regulatory-factor-network-predicts-their-role-in-t-cell-activation
#5
Marta E Polak, Chuin Ying Ung, Joanna Masapust, Tom C Freeman, Michael R Ardern-Jones
Langerhans cells (LCs) are able to orchestrate adaptive immune responses in the skin by interpreting the microenvironmental context in which they encounter foreign substances, but the regulatory basis for this has not been established. Utilising systems immunology approaches combining in silico modelling of a reconstructed gene regulatory network (GRN) with in vitro validation of the predictions, we sought to determine the mechanisms of regulation of immune responses in human primary LCs. The key role of Interferon regulatory factors (IRFs) as controllers of the human Langerhans cell response to epidermal cytokines was revealed by whole transcriptome analysis...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28369076/transient-chromatin-properties-revealed-by-polymer-models-and-stochastic-simulations-constructed-from-chromosomal-capture-data
#6
Ofir Shukron, David Holcman
Chromatin organization can be probed by Chromosomal Capture (5C) data, from which the encounter probability (EP) between genomic sites is presented in a large matrix. This matrix is averaged over a large cell population, revealing diagonal blocks called Topological Associating Domains (TADs) that represent a sub-chromatin organization. To study the relation between chromatin organization and gene regulation, we introduce a computational procedure to construct a bead-spring polymer model based on the EP matrix...
April 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28355056/deconvolution-of-gene-expression-noise-into-spatial-dynamics-of-transcription-factor-promoter-interplay
#7
Ángel Goñi-Moreno, Ilaria Benedetti, Juhyun Kim, Víctor de Lorenzo
Gene expression noise is not only the mere consequence of stochasticity, but also a signal that reflects the upstream physical dynamics of the cognate molecular machinery. Soil bacteria facing recalcitrant pollutants exploit noise of catabolic promoters to deploy beneficial phenotypes such as metabolic bet-hedging and/or division of biochemical labor. Although the role of upstream promoter-regulator interplay in the origin of this noise is little understood, its specifications are probably ciphered in flow cytometry data patterns...
April 17, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28352251/stochastic-and-differential-activation-of-%C3%AF-b-and-prfa-in-listeria-monocytogenes-at-the-single-cell-level-under-different-environmental-stress-conditions
#8
Claudia Guldimann, Veronica Guariglia-Oropeza, Sophia Harrand, David Kent, Kathryn J Boor, Martin Wiedmann
During host infection, the foodborne pathogen Listeria monocytogenes must sense and respond to rapidly changing environmental conditions. Two transcriptional regulators, the alternative sigma factor B (σ(B)) and the Positive Regulatory Factor A (PrfA), are key contributors to the transcriptomic responses that enable bacterial survival in the host gastrointestinal tract and invasion of host duodenal cells. Increases in temperature and osmolarity induce activity of these proteins; such conditions may be encountered in food matrices as well as within the host gastrointestinal tract...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28341132/stochastic-modeling-and-numerical-simulation-of-gene-regulatory-networks-with-protein-bursting
#9
Manuel Pájaro, Antonio A Alonso, Irene Otero-Muras, Carlos Vázquez
Gene expression is inherently stochastic. Advanced single-cell microscopy techniques together with mathematical models for single gene expression led to important insights in elucidating the sources of intrinsic noise in prokaryotic and eukaryotic cells. In addition to the finite size effects due to low copy numbers, translational bursting is a dominant source of stochasticity in cell scenarios involving few short lived mRNA transcripts with high translational efficiency (as is typically the case for prokaryotes), causing protein synthesis to occur in random bursts...
March 21, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28320934/allele-specific-non-cg-dna-methylation-marks-domains-of-active-chromatin-in-female-mouse-brain
#10
Christopher L Keown, Joel B Berletch, Rosa Castanon, Joseph R Nery, Christine M Disteche, Joseph R Ecker, Eran A Mukamel
DNA methylation at gene promoters in a CG context is associated with transcriptional repression, including at genes silenced on the inactive X chromosome in females. Non-CG methylation (mCH) is a distinct feature of the neuronal epigenome that is differentially distributed between males and females on the X chromosome. However, little is known about differences in mCH on the active (Xa) and inactive (Xi) X chromosomes because stochastic X-chromosome inactivation (XCI) confounds allele-specific epigenomic profiling...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28289838/a-stochastic-analysis-of-autoregulation-of-gene-expression
#11
Renaud Dessalles, Vincent Fromion, Philippe Robert
This paper analyzes, in the context of a prokaryotic cell, the stochastic variability of the number of proteins when there is a control of gene expression by an autoregulation scheme. The goal of this work is to estimate the efficiency of the regulation to limit the fluctuations of the number of copies of a given protein. The autoregulation considered in this paper relies mainly on a negative feedback: the proteins are repressors of their own gene expression. The efficiency of a production process without feedback control is compared to a production process with an autoregulation of the gene expression assuming that both of them produce the same average number of proteins...
March 13, 2017: Journal of Mathematical Biology
https://www.readbyqxmd.com/read/28288800/determining-the-limitations-and-benefits-of-noise-in-gene-regulation-and-signal-transduction-through-single-cell-microscopy-based-analysis
#12
REVIEW
Marie D Harton, Eric Batchelor
Stochastic fluctuations, termed "noise," in the level of biological molecules can greatly impact cellular functions. While biological noise can sometimes be detrimental, recent studies have provided an increasing number of examples in which biological noise can be functionally beneficial. Rather than provide an exhaustive review of the growing literature in this field, in this review, we focus on single-cell studies based on quantitative microscopy that have generated a deeper understanding of the sources, characteristics, limitations, and benefits of biological noise...
March 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28219439/rnas-competing-for-micrornas-mutually-influence-their-fluctuations-in-a-highly-non-linear-microrna-dependent-manner-in-single-cells
#13
Carla Bosia, Francesco Sgrò, Laura Conti, Carlo Baldassi, Davide Brusa, Federica Cavallo, Ferdinando Di Cunto, Emilia Turco, Andrea Pagnani, Riccardo Zecchina
BACKGROUND: Distinct RNA species may compete for binding to microRNAs (miRNAs). This competition creates an indirect interaction between miRNA targets, which behave as miRNA sponges and eventually influence each other's expression levels. Theoretical predictions suggest that not only the mean expression levels of targets but also the fluctuations around the means are coupled through miRNAs. This may result in striking effects on a broad range of cellular processes, such as cell differentiation and proliferation...
February 20, 2017: Genome Biology
https://www.readbyqxmd.com/read/28208380/inferring-hidden-states-in-langevin-dynamics-on-large-networks-average-case-performance
#14
B Bravi, M Opper, P Sollich
We present average performance results for dynamical inference problems in large networks, where a set of nodes is hidden while the time trajectories of the others are observed. Examples of this scenario can occur in signal transduction and gene regulation networks. We focus on the linear stochastic dynamics of continuous variables interacting via random Gaussian couplings of generic symmetry. We analyze the inference error, given by the variance of the posterior distribution over hidden paths, in the thermodynamic limit and as a function of the system parameters and the ratio α between the number of hidden and observed nodes...
January 2017: Physical Review. E
https://www.readbyqxmd.com/read/28202515/systematic-in-vivo-inactivation-of-chromatin-regulating-enzymes-identifies-setd2-as-a-potent-tumor-suppressor-in-lung-adenocarcinoma
#15
David M Walter, Olivia S Venancio, Elizabeth L Buza, John W Tobias, Charuhas Deshpande, A Andrea Gudiel, Caroline Kim-Kiselak, Michelle Cicchini, Travis J Yates, David M Feldser
Chromatin-modifying genes are frequently mutated in human lung adenocarcinoma, but the functional impact of these mutations on disease initiation and progression is not well understood. Using a CRISPR-based approach, we systematically inactivated three of the most commonly mutated chromatin regulatory genes in two Kras(G12D)-driven mouse models of lung adenocarcinoma to characterize the impact of their loss. Targeted inactivation of SWI/SNF nucleosome-remodeling complex members Smarca4 (Brg1) or Arid1a had complex effects on lung adenocarcinoma initiation and progression...
April 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28176840/the-dynamic-mechanism-of-noisy-signal-decoding-in-gene-regulation
#16
Peijiang Liu, Haohua Wang, Lifang Huang, Tianshou Zhou
Experimental evidence supports that signaling pathways can induce different dynamics of transcription factor (TF) activation, but how an input signal is encoded by such a dynamic, noisy TF and further decoded by downstream genes remains largely unclear. Here, using a system of stochastic transcription with signal regulation, we show that (1) keeping the intensity of the signal noise invariant but prolonging the signal duration can both enhance the mutual information (MI) and reduce the energetic cost (EC); (2) if the signal duration is fixed, the larger MI needs the larger EC, but if the signal period is fixed, there is an optimal time that the signal spends at one lower branch, such that MI reaches the maximum; (3) if both the period and the duration are simultaneously fixed, increasing the input noise can always enhance MI in the case of transcription regulation rather than in the case of degradation regulation...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28166778/markov-state-models-of-gene-regulatory-networks
#17
Brian K Chu, Margaret J Tse, Royce R Sato, Elizabeth L Read
BACKGROUND: Gene regulatory networks with dynamics characterized by multiple stable states underlie cell fate-decisions. Quantitative models that can link molecular-level knowledge of gene regulation to a global understanding of network dynamics have the potential to guide cell-reprogramming strategies. Networks are often modeled by the stochastic Chemical Master Equation, but methods for systematic identification of key properties of the global dynamics are currently lacking. RESULTS: The method identifies the number, phenotypes, and lifetimes of long-lived states for a set of common gene regulatory network models...
February 6, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28135279/cell-sorting-and-noise-induced-cell-plasticity-coordinate-to-sharpen-boundaries-between-gene-expression-domains
#18
Qixuan Wang, William R Holmes, Julian Sosnik, Thomas Schilling, Qing Nie
A fundamental question in biology is how sharp boundaries of gene expression form precisely in spite of biological variation/noise. Numerous mechanisms position gene expression domains across fields of cells (e.g. morphogens), but how these domains are refined remains unclear. In some cases, domain boundaries sharpen through differential adhesion-mediated cell sorting. However, boundaries can also sharpen through cellular plasticity, with cell fate changes driven by up- or down-regulation of gene expression...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28130236/h-o-ta-estimation-of-dna-methylation-and-hydroxylation-levels-and-efficiencies-from-time-course-data
#19
Charalampos Kyriakopoulos, Pascal Giehr, Verena Wolf
MOTIVATION: Methylation and hydroxylation of cytosines to form 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) belong to the most important epigenetic modifications and their vital role in the regulation of gene expression has been widely recognized. Recent experimental techniques allow to infer methylation and hydroxylation levels at CpG dinucleotides but require a sophisticated statistical analysis to achieve accurate estimates. RESULTS: We present H(O)TA, a software tool based on a stochastic modeling approach, which simultaneously analyzes time course data from hairpin bisulfite sequencing and hairpin oxidative bisulfite sequencing...
January 27, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28115210/the-methylation-of-nuclear-and-mitochondrial-dna-in-ageing-phenotypes-and-longevity
#20
REVIEW
Maria Giulia Bacalini, Patrizia D'Aquila, Elena Marasco, Christine Nardini, Alberto Montesanto, Claudio Franceschi, Giuseppe Passarino, Paolo Garagnani, Dina Bellizzi
An increasing body of data is progressively indicating that the comprehension of the epigenetic landscape, actively integrated with the genetic elements, is crucial to delineate the molecular basis of the inter-individual complexity of ageing process. Indeed, it has emerged that DNA methylation changes occur during ageing, consisting mainly in a progressive process of genome demethylation, in a hypermethylation of gene-specific CpG dinucleotides, as well as in an inter-individual divergence of the epigenome due to stochastic events and environmental exposures throughout life, namely as epigenetic drift...
January 20, 2017: Mechanisms of Ageing and Development
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