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Stochastic gene regulation

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https://www.readbyqxmd.com/read/28641269/a-model-based-tool-for-the-analysis-and-design-of-gene-regulatory-network
#1
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
#2
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
#3
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 7, 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
#4
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
#5
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 5, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28581725/engineered-control-of-genetic-variability-reveals-interplay-between-quorum-sensing-feedback-regulation-and-biochemical-noise
#6
Yadira Boada, Alejandro Vignoni, Jesus Pico
Stochastic fluctuations in gene expression trigger both beneficial and harmful consequences for cell behavior. Therefore, achieving a desired mean protein expression level while minimizing noise is of interest in many applications, including robust protein production systems in industrial biotechnology. Here we consider a synthetic gene circuit combining intracellular negative feedback and cell-to-cell communication based on quorum sensing. Accounting for both intrinsic and extrinsic noise, stochastic simulations allow us to analyze the capability of the circuit to reduce noise strength as a function of its parameters...
June 5, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28573295/what-shapes-eukaryotic-transcriptional-bursting
#7
REVIEW
Damien Nicolas, Nick E Phillips, Felix Naef
Isogenic cells in a common environment present a large degree of heterogeneity in gene expression. Part of this variability is attributed to transcriptional bursting: the stochastic activation and inactivation of promoters that leads to the discontinuous production of mRNA. The diversity in bursting patterns displayed by different genes suggests the existence of a connection between bursting and gene regulation. Experimental strategies such as single-molecule RNA FISH, MS2-GFP or short-lived protein reporters allow the quantification of transcriptional bursting and the comparison of bursting kinetics between conditions, allowing therefore the identification of molecular mechanisms modulating transcriptional bursting...
June 2, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28571483/an-efficient-method-for-significant-motifs-discovery-from-multiple-dna-sequences
#8
Abdulrakeeb M Al-Ssulami, Aqil M Azmi, Hassan Mathkour
Identification of transcription factor binding sites or biological motifs is an important step in deciphering the mechanisms of gene regulation. It is a classic problem that has eluded a satisfactory and efficient solution. In this paper, we devise a three-phase algorithm to mine for biologically significant motifs. In the first phase, we generate all the possible string motifs, this phase is followed by a filtering process where we discard all motifs that do not meet the constraints. And in the final phase, motifs are scored and ranked using a combination of stochastic techniques and [Formula: see text]-value...
May 11, 2017: Journal of Bioinformatics and Computational Biology
https://www.readbyqxmd.com/read/28555639/clonally-stable-v%C3%AE%C2%BA-allelic-choice-instructs-ig%C3%AE%C2%BA-repertoire
#9
Rena Levin-Klein, Shira Fraenkel, Michal Lichtenstein, Louise S Matheson, Osnat Bartok, Yuval Nevo, Sebastian Kadener, Anne E Corcoran, Howard Cedar, Yehudit Bergman
Although much has been done to understand how rearrangement of the Igκ locus is regulated during B-cell development, little is known about the way the variable (V) segments themselves are selected. Here we show, using B6/Cast hybrid pre-B-cell clones, that a limited number of V segments on each allele is stochastically activated as characterized by the appearance of non-coding RNA and histone modifications. The activation states are clonally distinct, stable across cell division and developmentally important in directing the Ig repertoire upon differentiation...
May 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28523547/dna-methylation-in-major-depressive-disorder
#10
Ehsan Pishva, Bart P F Rutten, Daniel van den Hove
Epigenetic mechanisms regulate gene expression, influencing protein levels and ultimately shaping phenotypes during life. However, both stochastic epigenetic variations and environmental reprogramming of the epigenome might influence neurodevelopment and ageing, and this may contribute to the origins of mental ill-health. Studying the role of epigenetic mechanisms is challenging, as genotype-, tissue- and cell type-dependent epigenetic changes have to be taken into account, while the nature of mental disorders also poses significant challenges for linking them with biological profiles...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28514750/epigenome-wide-association-study-in-hepatocellular-carcinoma-identification-of-stochastic-epigenetic-mutations-through-an-innovative-statistical-approach
#11
Davide Gentilini, Stefania Scala, Germano Gaudenzi, Paolo Garagnani, Miriam Capri, Matteo Cescon, Gian Luca Grazi, Maria Giulia Bacalini, Serena Pisoni, Alessandra Dicitore, Luisa Circelli, Sara Santagata, Francesco Izzo, Anna Maria Di Blasio, Luca Persani, Claudio Franceschi, Giovanni Vitale
Hepatocellular carcinoma (HCC) results from accumulation of both genetic and epigenetic alterations. We investigated the genome-wide DNA methylation profile in 69 pairs of HCC and adjacent non-cancerous liver tissues using the Infinium HumanMethylation 450K BeadChip array. An innovative analytical approach has been adopted to identify Stochastic Epigenetic Mutations (SEMs) in HCC.HCC and peritumoral tissues showed a different epigenetic profile, mainly characterized by loss of DNA methylation in HCC. Total number of SEMs was significantly higher in HCC tumor (median: 77,370) than in peritumoral (median: 5,656) tissues and correlated with tumor grade...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28511648/a-mathematical-model-of-mechanotransduction-reveals-how-mechanical-memory-regulates-mesenchymal-stem-cell-fate-decisions
#12
Tao Peng, Linan Liu, Adam L MacLean, Chi Wut Wong, Weian Zhao, Qing Nie
BACKGROUND: Mechanical and biophysical properties of the cellular microenvironment regulate cell fate decisions. Mesenchymal stem cell (MSC) fate is influenced by past mechanical dosing (memory), but the mechanisms underlying this process have not yet been well defined. We have yet to understand how memory affects specific cell fate decisions, such as the differentiation of MSCs into neurons, adipocytes, myocytes, and osteoblasts. RESULTS: We study a minimal gene regulatory network permissive of multi-lineage MSC differentiation into four cell fates...
May 16, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28498984/inheritance-of-vernalization-memory-at-flowering-locus-c-during-plant-regeneration
#13
Miyuki Nakamura, Lars Hennig
Specific gene states can be transmitted to subsequent cell generations through mitosis involving particular chromatin (epigenetic) states. During reproduction of plants and animals, however, most epigenetic states are reset to allow development to start anew. Flowering is one of the critical developmental steps by which plants acquire their reproductive capacity. This phase transition is controlled by environmental signals and autonomous regulation. The FLOWERING LOCUS C (FLC) gene is a flowering repressor that is epigenetically silenced after long-term exposure to cold, ensuring flowering in the spring season...
May 11, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28495919/alternative-tsss-are-co-regulated-in-single-cells-in-the-mouse-brain
#14
Kasper Karlsson, Peter Lönnerberg, Sten Linnarsson
Alternative transcription start sites (TSSs) have been extensively studied genome-wide for many cell types and have been shown to be important during development and to regulate transcript abundance between cell types. Likewise, single-cell gene expression has been extensively studied for many cell types. However, how single cells use TSSs has not yet been examined. In particular, it is unknown whether alternative TSSs are independently expressed, or whether they are co-activated or even mutually exclusive in single cells...
May 11, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28493880/identifying-stochastic-oscillations-in-single-cell-live-imaging-time-series-using-gaussian-processes
#15
Nick E Phillips, Cerys Manning, Nancy Papalopulu, Magnus Rattray
Multiple biological processes are driven by oscillatory gene expression at different time scales. Pulsatile dynamics are thought to be widespread, and single-cell live imaging of gene expression has lead to a surge of dynamic, possibly oscillatory, data for different gene networks. However, the regulation of gene expression at the level of an individual cell involves reactions between finite numbers of molecules, and this can result in inherent randomness in expression dynamics, which blurs the boundaries between aperiodic fluctuations and noisy oscillators...
May 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28483564/the-influence-of-nuclear-compartmentalisation-on-stochastic-dynamics-of-self-repressing-gene-expression
#16
Marc Sturrock, Shiyu Li, Vahid Shahrezaei
Gene expression is an inherently noisy process. This noise is generally thought to be deleterious as precise internal regulation of biochemical reactions is essential for cell growth and survival. Self-repression of gene expression, which is the simplest form of a negative feedback loop, is commonly believed to be employed by cellular systems to decrease the stochastic fluctuations in gene expression. When there is some delay in autoregulation, it is also believed that this system can generate oscillations...
May 5, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28469006/shaping-development-by-stochasticity-and-dynamics-in-gene-regulation
#17
REVIEW
Peng Dong, Zhe Liu
Animal development is orchestrated by spatio-temporal gene expression programmes that drive precise lineage commitment, proliferation and migration events at the single-cell level, collectively leading to large-scale morphological change and functional specification in the whole organism. Efforts over decades have uncovered two 'seemingly contradictory' mechanisms in gene regulation governing these intricate processes: (i) stochasticity at individual gene regulatory steps in single cells and (ii) highly coordinated gene expression dynamics in the embryo...
May 2017: Open Biology
https://www.readbyqxmd.com/read/28437444/transcriptional-bursting-in-drosophila-development-stochastic-dynamics-of-eve-stripe-2-expression
#18
David M Holloway, Alexander V Spirov
Anterior-posterior (AP) body segmentation of the fruit fly (Drosophila) is first seen in the 7-stripe spatial expression patterns of the pair-rule genes, which regulate downstream genes determining specific segment identities. Regulation of pair-rule expression has been extensively studied for the even-skipped (eve) gene. Recent live imaging, of a reporter for the 2nd eve stripe, has demonstrated the stochastic nature of this process, with 'bursts' in the number of RNA transcripts being made over time. We developed a stochastic model of the spatial and temporal expression of eve stripe 2 (binding by transcriptional activators (Bicoid and Hunchback proteins) and repressors (Giant and Krüppel proteins), transcriptional initiation and termination; with all rate parameters constrained by features of the experimental data) in order to analyze the noisy experimental time series and test hypotheses for how eve transcription is regulated...
2017: PloS One
https://www.readbyqxmd.com/read/28427910/stochasticity-of-gene-expression-as-a-motor-of-epigenetics-in-bacteria-from-individual-to-collective-behaviors
#19
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. Gene expression noise 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 a 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
#20
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 2017: PLoS Computational Biology
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