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Stochastic gene regulation

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https://www.readbyqxmd.com/read/28523547/dna-methylation-in-major-depressive-disorder
#1
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
#2
REVIEW
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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-behavior
#10
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
#11
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
https://www.readbyqxmd.com/read/28402875/tracking-low-copy-transcription-factors-in-living-bacteria-the-case-of-the-lac-repressor
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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