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Stochastic gene regulation

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https://www.readbyqxmd.com/read/28809965/hill-kinetics-as-a-noise-filter-the-role-of-transcription-factor-autoregulation-in-gene-cascades
#1
Anna Ochab-Marcinek, Jakub Jędrak, Marcin Tabaka
An intuition based on deterministic models of chemical kinetics is that population heterogeneity of transcription factor levels in cells is transmitted unchanged downstream to the target genes. We use a stochastic model of a two-gene cascade with a self-regulating upstream gene to show that, counter to the intuition, there is no simple mapping (bimodal to bimodal, unimodal to unimodal) between the shapes of the distributions of transcription factor numbers and target protein numbers in cells. Due to the presence of the two regulations, the system contains two nonlinear transfer functions, defined by the Hill kinetics of transcription factor binding...
August 15, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28799233/stochastics-of-cellular-differentiation-explained-by-epigenetics-the-case-of-t-cell-differentiation-and-functional-plasticity
#2
REVIEW
Jaydeep Bhat, Johannes Helmuth, Guranda Chitadze, Léonce Kouakanou, Christian Peters, Martin Vingron, Ole Ammerpohl, Dieter Kabelitz
Epigenetic marks including histone modifications and DNA methylation are associated to the regulation of gene expression and activity. In addition, an increasing number of non-coding RNAs with regulatory activity on gene expression have been identified. Alongside, technological advancements allow for the analysis of these mechanisms with high resolution - up to the single-cell level. For instance, the assay for transposase-accessible chromatin using sequencing (ATAC-seq) simultaneously probes for chromatin accessibility and nucleosome positioning...
August 10, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28790204/bacterial-chromatin-structural-proteins-regulate-the-bimodal-expression-of-the-locus-of-enterocyte-effacement-lee-pathogenicity-island-in-enteropathogenic-escherichia-coli
#3
Hervé Leh, Ahmad Khodr, Marie-Christine Bouger, Bianca Sclavi, Sylvie Rimsky, Stéphanie Bury-Moné
In enteropathogenic Escherichia coli (EPEC), the locus of enterocyte effacement (LEE) encodes a type 3 secretion system (T3SS) essential for pathogenesis. This pathogenicity island comprises five major operons (LEE1 to LEE5), with the LEE5 operon encoding T3SS effectors involved in the intimate adherence of bacteria to enterocytes. The first operon, LEE1, encodes Ler (LEE-encoded regulator), an H-NS (nucleoid structuring protein) paralog that alleviates the LEE H-NS silencing. We observed that the LEE5 and LEE1 promoters present a bimodal expression pattern, depending on environmental stimuli...
August 8, 2017: MBio
https://www.readbyqxmd.com/read/28741470/ecological-feedback-in-quorum-sensing-microbial-populations-can-induce-heterogeneous-production-of-autoinducers
#4
Matthias Bauer, Johannes Knebel, Matthias Lechner, Peter Pickl, Erwin Frey
Autoinducers are small signaling molecules that mediate intercellular communication in microbial populations and trigger coordinated gene expression via 'quorum sensing'. Elucidating the mechanisms that control autoinducer production is, thus, pertinent to understanding collective microbial behavior, such as virulence and bioluminescence. Recent experiments have shown a heterogeneous promoter activity of autoinducer synthase genes, suggesting that some of the isogenic cells in a population might produce autoinducers, whereas others might not...
July 25, 2017: ELife
https://www.readbyqxmd.com/read/28724976/gene-expression-reversal-toward-pre-adult-levels-in-the-aging-human-brain-and-age-related-loss-of-cellular-identity
#5
Handan Melike Dönertaş, Hamit İzgi, Altuğ Kamacıoğlu, Zhisong He, Philipp Khaitovich, Mehmet Somel
It was previously reported that mRNA expression levels in the prefrontal cortex at old age start to resemble pre-adult levels. Such expression reversals could imply loss of cellular identity in the aging brain, and provide a link between aging-related molecular changes and functional decline. Here we analyzed 19 brain transcriptome age-series datasets, comprising 17 diverse brain regions, to investigate the ubiquity and functional properties of expression reversal in the human brain. Across all 19 datasets, 25 genes were consistently up-regulated during postnatal development and down-regulated in aging, displaying an "up-down" pattern that was significant as determined by random permutations...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28719044/symmetry-breaking-in-development-and-stochastic-gene-expression
#6
REVIEW
Jonathan R Chubb
The prevailing emphasis in developmental biology since the expansion of the molecular biology age has been that developmental decisions are instructive. A cell differentiates to become a specific cell type because it receives a signal, whereas its neighbor that does not receive the signal adopts a different fate. This emphasis has been generally accepted, largely because of the success of this view in tractable invertebrate model organisms, and the widespread similarities in molecular regulation to the development of more complex species...
July 18, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28715961/genetics-and-epigenetics-of-mating-type-determination-in-paramecium-and-tetrahymena
#7
Eduardo Orias, Deepankar Pratap Singh, Eric Meyer
While sex is an ancient and highly conserved eukaryotic invention, self-incompatibility systems such as mating types or sexes appear to be derived limitations that show considerable evolutionary plasticity. Within a single class of ciliates, Paramecium and Tetrahymena species have long been known to present a wide variety of mating type numbers and modes of inheritance, but only recently have the genes involved been identified. Although similar transmembrane proteins mediate self/nonself recognition in both ciliates, the mechanisms of mating type determination differ widely, ranging from Mendelian systems to developmental nuclear differentiation, either stochastic or maternally inherited...
July 17, 2017: Annual Review of Microbiology
https://www.readbyqxmd.com/read/28700688/four-simple-rules-that-are-sufficient-to-generate-the-mammalian-blastocyst
#8
Silas Boye Nissen, Marta Perera, Javier Martin Gonzalez, Sophie M Morgani, Mogens H Jensen, Kim Sneppen, Joshua M Brickman, Ala Trusina
Early mammalian development is both highly regulative and self-organizing. It involves the interplay of cell position, predetermined gene regulatory networks, and environmental interactions to generate the physical arrangement of the blastocyst with precise timing. However, this process occurs in the absence of maternal information and in the presence of transcriptional stochasticity. How does the preimplantation embryo ensure robust, reproducible development in this context? It utilizes a versatile toolbox that includes complex intracellular networks coupled to cell-cell communication, segregation by differential adhesion, and apoptosis...
July 2017: PLoS Biology
https://www.readbyqxmd.com/read/28671948/stochasticity-in-the-enterococcal-sex-pheromone-response-revealed-by-quantitative-analysis-of-transcription-in-single-cells
#9
Rebecca J Breuer, Arpan Bandyopadhyay, Sofie A O'Brien, Aaron M T Barnes, Ryan C Hunter, Wei-Shou Hu, Gary M Dunny
In Enterococcus faecalis, sex pheromone-mediated transfer of antibiotic resistance plasmids can occur under unfavorable conditions, for example, when inducing pheromone concentrations are low and inhibiting pheromone concentrations are high. To better understand this paradox, we adapted fluorescence in situ hybridization chain reaction (HCR) methodology for simultaneous quantification of multiple E. faecalis transcripts at the single cell level. We present direct evidence for variability in the minimum period, maximum response level, and duration of response of individual cells to a specific inducing condition...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28671686/the-methyltransferase-setdb1-regulates-a-large-neuron-specific-topological-chromatin-domain
#10
Yan Jiang, Yong-Hwee Eddie Loh, Prashanth Rajarajan, Teruyoshi Hirayama, Will Liao, Bibi S Kassim, Behnam Javidfar, Brigham J Hartley, Lisa Kleofas, Royce B Park, Benoit Labonte, Seok-Man Ho, Sandhya Chandrasekaran, Catherine Do, Brianna R Ramirez, Cyril J Peter, Julia T C W, Brian M Safaie, Hirofumi Morishita, Panos Roussos, Eric J Nestler, Anne Schaefer, Benjamin Tycko, Kristen J Brennand, Takeshi Yagi, Li Shen, Schahram Akbarian
We report locus-specific disintegration of megabase-scale chromosomal conformations in brain after neuronal ablation of Setdb1 (also known as Kmt1e; encodes a histone H3 lysine 9 methyltransferase), including a large topologically associated 1.2-Mb domain conserved in humans and mice that encompasses >70 genes at the clustered protocadherin locus (hereafter referred to as cPcdh). The cPcdh topologically associated domain (TAD(cPcdh)) in neurons from mutant mice showed abnormal accumulation of the transcriptional regulator and three-dimensional (3D) genome organizer CTCF at cryptic binding sites, in conjunction with DNA cytosine hypomethylation, histone hyperacetylation and upregulated expression...
August 2017: Nature Genetics
https://www.readbyqxmd.com/read/28667450/review-of-stochastic-hybrid-systems-with-applications-in-biological-systems-modeling-and-analysis
#11
REVIEW
Xiangfang Li, Oluwaseyi Omotere, Lijun Qian, Edward R Dougherty
Stochastic hybrid systems (SHS) have attracted a lot of research interests in recent years. In this paper, we review some of the recent applications of SHS to biological systems modeling and analysis. Due to the nature of molecular interactions, many biological processes can be conveniently described as a mixture of continuous and discrete phenomena employing SHS models. With the advancement of SHS theory, it is expected that insights can be obtained about biological processes such as drug effects on gene regulation...
December 2017: EURASIP Journal on Bioinformatics & Systems Biology
https://www.readbyqxmd.com/read/28667253/inhibitors-alter-the-stochasticity-of-regulatory-proteins-to-force-cells-to-switch-to-the-other-state-in-the-bistable-system
#12
Wun-Sin Jhang, Shih-Chiang Lo, Chen-Chao Yeh, Che-Chi Shu
The cellular behaviors under the control of genetic circuits are subject to stochastic fluctuations, or noise. The stochasticity in gene regulation, far from a nuisance, has been gradually appreciated for its unusual function in cellular activities. In this work, with Chemical Master Equation (CME), we discovered that the addition of inhibitors altered the stochasticity of regulatory proteins. For a bistable system of a mutually inhibitory network, such a change of noise led to the migration of cells in the bimodal distribution...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28665997/independent-regulation-of-gene-expression-level-and-noise-by-histone-modifications
#13
Shaohuan Wu, Ke Li, Yingshu Li, Tong Zhao, Ting Li, Yu-Fei Yang, Wenfeng Qian
The inherent stochasticity generates substantial gene expression variation among isogenic cells under identical conditions, which is frequently referred to as gene expression noise or cell-to-cell expression variability. Similar to (average) expression level, expression noise is also subject to natural selection. Yet it has been observed that noise is negatively correlated with expression level, which manifests as a potential constraint for simultaneous optimization of both. Here, we studied expression noise in human embryonic cells with computational analysis on single-cell RNA-seq data and in yeast with flow cytometry experiments...
June 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28661893/exact-lower-and-upper-bounds-on-stationary-moments-in-stochastic-biochemical-systems
#14
Khem Raj Ghusinga, Cesar A Vargas-Garcia, Andrew Lamperski, Abhyudai Singh
In the stochastic description of biochemical reaction systems, the time evolution of statistical moments for species population counts is described by a linear dynamical system. However, except for some ideal cases (such as zero- and first-order reaction kinetics), the moment dynamics is underdetermined as lower-order moments depend upon higher-order moments. Here, we propose a novel method to find exact lower and upper bounds on stationary moments for a given arbitrary system of biochemical reactions. The method exploits the fact that statistical moments of any positive-valued random variable must satisfy some constraints that are compactly represented through the positive semidefiniteness of moment matrices...
June 29, 2017: Physical Biology
https://www.readbyqxmd.com/read/28652613/flipping-between-polycomb-repressed-and-active-transcriptional-states-introduces-noise-in-gene-expression
#15
Gozde Kar, Jong Kyoung Kim, Aleksandra A Kolodziejczyk, Kedar Nath Natarajan, Elena Torlai Triglia, Borbala Mifsud, Sarah Elderkin, John C Marioni, Ana Pombo, Sarah A Teichmann
Polycomb repressive complexes (PRCs) are important histone modifiers, which silence gene expression; yet, there exists a subset of PRC-bound genes actively transcribed by RNA polymerase II (RNAPII). It is likely that the role of Polycomb repressive complex is to dampen expression of these PRC-active genes. However, it is unclear how this flipping between chromatin states alters the kinetics of transcription. Here, we integrate histone modifications and RNAPII states derived from bulk ChIP-seq data with single-cell RNA-sequencing data...
June 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28641269/a-model-based-tool-for-the-analysis-and-design-of-gene-regulatory-network
#16
Liliana Ironi, Ettore Lanzarone
Computational and mathematical models have significantly contributed to the rapid progress in the study of gene regulatory networks (GRN), but researchers still lack a reliable model-based framework for computer-aided analysis and design. Such tool should both reveal the relation between network structure and dynamics and find parameter values and/or constraints that enable the simulated dynamics to reproduce specific behaviors. This paper addresses these issues and proposes a computational framework that facilitates network analysis or design...
June 19, 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28591566/regulation-of-clustered-protocadherin-genes-in-individual-neurons
#17
REVIEW
Teruyoshi Hirayama, Takeshi Yagi
Individual neurons are basic functional units in the complex system of the brain. One aspect of neuronal individuality is generated by stochastic and combinatorial expression of diverse clustered protocadherins (Pcdhs), encoded by the Pcdha, Pcdhb, and Pcdhg gene clusters, that are critical for several aspects of neural circuit formation. Each clustered Pcdh gene has its own promoter containing conserved sequences and is transcribed by a promoter choice mechanism involving interaction between the promoter and enhancers...
June 4, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28591515/roc-n-ribo-characterizing-a-riboswitching-expression-system-by-modeling-single-cell-data
#18
Christopher Schneider, Leo Bronstein, Jascha Diemer, Heinz Koeppl, Beatrix Suess
RNA-engineered systems offer simple and versatile control over gene expression in many organisms. In particular, the design and implementation of riboswitches presents a unique opportunity to manipulate any reporter device in cis, executing tight temporal and spatial control at low metabolic costs. Assembled to higher order genetic circuits, such riboswitch-regulated devices may efficiently process logical operations. Here, we propose a hierarchical stochastic modeling approach to characterize an in silico repressor gate based on neomycin- and tetracycline-sensitive riboswitches...
June 30, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28587744/mathematical-comparison-of-memory-functions-between-mutual-activation-and-repression-networks-in-a-stochastic-environment
#19
A B M Shamim Ul Hasan, Hiroyuki Kurata
Biological memory is a ubiquitous function that can generate a sustained response to a transient inductive stimulus. To better understand this function, we must consider the mechanisms by which different structures of genetic networks achieve memory. Here, we investigated two competitive gene regulatory network models: the regulated mutual activation network (MAN) and the regulated mutual repression network (MRN). Stochasticity deteriorated the persistence of memory of both the MAN and the MRN. Mathematical comparison by simulation and theoretical analysis identified functional differences in the stochastic memory between the competitive models: specifically, the MAN provided much more robust, persistent memory than the MRN...
June 3, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28582397/reduction-of-multiscale-stochastic-biochemical-reaction-networks-using-exact-moment-derivation
#20
Jae Kyoung Kim, Eduardo D Sontag
Biochemical reaction networks (BRNs) in a cell frequently consist of reactions with disparate timescales. The stochastic simulations of such multiscale BRNs are prohibitively slow due to high computational cost for the simulations of fast reactions. One way to resolve this problem uses the fact that fast species regulated by fast reactions quickly equilibrate to their stationary distribution while slow species are unlikely to be changed. Thus, on a slow timescale, fast species can be replaced by their quasi-steady state (QSS): their stationary conditional expectation values for given slow species...
June 2017: PLoS Computational Biology
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