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Stochastic gene regulation

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https://www.readbyqxmd.com/read/29040384/selansi-a-toolbox-for-simulation-of-stochastic-gene-regulatory-networks
#1
Manuel Pájaro, Irene Otero-Muras, Carlos Vázquez, Antonio A Alonso
Motivation: Gene regulation is inherently stochastic. In many applications concerning Systems and Synthetic Biology such as the reverse engineering and the de novo design of genetic circuits, stochastic effects (yet potentially crucial) are often neglected due to the high computational cost of stochastic simulations. With advances in these fields there is an increasing need of tools providing accurate approximations of the stochastic dynamics of gene regulatory networks (GRNs) with reduced computational effort...
October 11, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29030469/single-cell-gene-expression-analysis-reveals-regulators-of-distinct-cell-subpopulations-among-developing-human-neurons
#2
Jiaxu Wang, Piroon Jenjaroenpun, Akshay Bhinge, Vladimir Espinosa Angarica, Antonio Del Sol, Intawat Nookaew, Vladimir A Kuznetsov, Lawrence W Stanton
The stochastic dynamics and regulatory mechanisms that govern differentiation of individual human neural precursor cells (NPC) into mature neurons are currently not fully understood. Here, we used single-cell RNA-sequencing (scRNA-seq) of developing neurons to dissect/identify NPC subtypes and critical developmental stages of alternative lineage specifications. This study comprises an unsupervised, high-resolution strategy for identifying cell developmental bifurcations, tracking the stochastic transcript kinetics of the subpopulations, elucidating regulatory networks, and finding key regulators...
October 13, 2017: Genome Research
https://www.readbyqxmd.com/read/29025390/partitioning-of-functional-gene-expression-data-using-principal-points
#3
Jaehee Kim, Haseong Kim
BACKGROUND: DNA microarrays offer motivation and hope for the simultaneous study of variations in multiple genes. Gene expression is a temporal process that allows variations in expression levels with a characterized gene function over a period of time. Temporal gene expression curves can be treated as functional data since they are considered as independent realizations of a stochastic process. This process requires appropriate models to identify patterns of gene functions. The partitioning of the functional data can find homogeneous subgroups of entities for the massive genes within the inherent biological networks...
October 12, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28977492/dna-residence-time-is-a-regulatory-factor-of-transcription-repression
#4
Karen Clauß, Achim P Popp, Lena Schulze, Johannes Hettich, Matthias Reisser, Laura Escoter Torres, N Henriette Uhlenhaut, J Christof M Gebhardt
Transcription comprises a highly regulated sequence of intrinsically stochastic processes, resulting in bursts of transcription intermitted by quiescence. In transcription activation or repression, a transcription factor binds dynamically to DNA, with a residence time unique to each factor. Whether the DNA residence time is important in the transcription process is unclear. Here, we designed a series of transcription repressors differing in their DNA residence time by utilizing the modular DNA binding domain of transcription activator-like effectors (TALEs) and varying the number of nucleotide-recognizing repeat domains...
August 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28968704/sincerities-inferring-gene-regulatory-networks-from-time-stamped-single-cell-transcriptional-expression-profiles
#5
Nan Papili Gao, S M Minhaz Ud-Dean, Olivier Gandrillon, Rudiyanto Gunawan
Motivation: Single cell transcriptional profiling opens up a new avenue in studying the functional role of cell-to-cell variability in physiological processes. The analysis of single cell expression profiles creates new challenges due to the distributive nature of the data and the stochastic dynamics of gene transcription process. The reconstruction of gene regulatory networks (GRNs) using single cell transcriptional profiles is particularly challenging, especially when directed gene-gene relationships are desired...
September 14, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28947742/noise-reduction-as-an-emergent-property-of-single-cell-aging
#6
Ping Liu, Ruijie Song, Gregory L Elison, Weilin Peng, Murat Acar
Noise-induced heterogeneity in gene expression is an inherent reality for cells. However, it is not well understood how noise strength changes for a single gene while the host cell is aging. Using a state-of-the-art microfluidic platform, we measure noise dynamics in aging yeast cells by tracking the generation-specific activity of the canonical GAL1 promoter. We observe noise reduction during normal aging of a cell, followed by a short catastrophe phase in which noise increased. We hypothesize that aging-associated increases in chromatin state transitions are behind the observed noise reduction and a stochastic model provides quantitative support to the proposed mechanism...
September 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28938803/hybrid-models-for-chemical-reaction-networks-multiscale-theory-and-application-to-gene-regulatory-systems
#7
Stefanie Winkelmann, Christof Schütte
Well-mixed stochastic chemical kinetics are properly modeled by the chemical master equation (CME) and associated Markov jump processes in molecule number space. If the reactants are present in large amounts, however, corresponding simulations of the stochastic dynamics become computationally expensive and model reductions are demanded. The classical model reduction approach uniformly rescales the overall dynamics to obtain deterministic systems characterized by ordinary differential equations, the well-known mass action reaction rate equations...
September 21, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28878283/rate-limiting-steps-in-transcription-dictate-sensitivity-to-variability-in-cellular-components
#8
Jarno Mäkelä, Vinodh Kandavalli, Andre S Ribeiro
Cell-to-cell variability in cellular components generates cell-to-cell diversity in RNA and protein production dynamics. As these components are inherited, this should also cause lineage-to-lineage variability in these dynamics. We conjectured that these effects on transcription are promoter initiation kinetics dependent. To test this, first we used stochastic models to predict that variability in the numbers of molecules involved in upstream processes, such as the intake of inducers from the environment, acts only as a transient source of variability in RNA production numbers, while variability in the numbers of a molecular species controlling transcription of an active promoter acts as a constant source...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28842224/an-efficient-and-assumption-free-method-to-approximate-protein-level-distribution-in-the-two-states-gene-expression-model
#9
Bingxiang Xu, Hao Ge, Zhihua Zhang
Stochastic fluctuations at each step of gene expression might influence protein levels distributions across cell populations. However, current methods to model protein distribution of intrinsic gene expression dynamics are either computationally inefficient or rely on ad hoc assumptions, e.g., that the gene is always active. Taking advantage of the simple form of lower-order moments of distribution, we developed an efficient and assumption-free protein distribution approximation method (EFPD), for the two state gene expression model to accurately approximate the distribution...
August 24, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28835372/pervasive-coexpression-of-spatially-proximal-genes-is-buffered-at-the-protein-level
#10
Georg Kustatscher, Piotr Grabowski, Juri Rappsilber
Genes are not randomly distributed in the genome. In humans, 10% of protein-coding genes are transcribed from bidirectional promoters and many more are organised in larger clusters. Intriguingly, neighbouring genes are frequently coexpressed but rarely functionally related. Here we show that coexpression of bidirectional gene pairs, and closeby genes in general, is buffered at the protein level. Taking into account the 3D architecture of the genome, we find that co-regulation of spatially close, functionally unrelated genes is pervasive at the transcriptome level, but does not extend to the proteome...
August 23, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28829770/combinatorial-regulation-of-a-blimp1-prdm1-enhancer-in-the-mouse-retina
#11
Taylor S Mills, Tatiana Eliseeva, Stephanie M Bersie, Grace Randazzo, Jhenya Nahreini, Ko Uoon Park, Joseph A Brzezinski
The mouse retina comprises seven major cell types that exist in differing proportions. They are generated from multipotent progenitors in a stochastic manner, such that the relative frequency of any given type generated changes over time. The mechanisms determining the proportions of each cell type are only partially understood. Photoreceptors and bipolar interneurons are derived from cells that express Otx2. Within this population, Blimp1 (Prdm1) helps set the balance between photoreceptors and bipolar cells by suppressing bipolar identity in most of the cells...
2017: PloS One
https://www.readbyqxmd.com/read/28809965/hill-kinetics-as-a-noise-filter-the-role-of-transcription-factor-autoregulation-in-gene-cascades
#12
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 23, 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
#13
REVIEW
J Bhat, J Helmuth, G Chitadze, L Kouakanou, C Peters, M Vingron, O Ammerpohl, D Kabelitz
Epigenetic marks including histone modifications and DNA methylation are associated with 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...
October 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
#14
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
#15
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
#16
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
#17
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...
November 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28715961/genetics-and-epigenetics-of-mating-type-determination-in-paramecium-and-tetrahymena
#18
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
#19
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
#20
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
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