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Stochastic gene regulation

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https://www.readbyqxmd.com/read/28341132/stochastic-modeling-and-numerical-simulation-of-gene-regulatory-networks-with-protein-bursting
#1
Manuel Pájaro, Antonio A Alonso, Irene Otero-Muras, C 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
#2
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...
March 20, 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
#3
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
#4
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 10, 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
#5
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
#6
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
#7
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 KrasG12D-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...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28176840/the-dynamic-mechanism-of-noisy-signal-decoding-in-gene-regulation
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28069947/first-passage-time-approach-to-controlling-noise-in-the-timing-of-intracellular-events
#13
Khem Raj Ghusinga, John J Dennehy, Abhyudai Singh
In the noisy cellular environment, gene products are subject to inherent random fluctuations in copy numbers over time. How cells ensure precision in the timing of key intracellular events despite such stochasticity is an intriguing fundamental problem. We formulate event timing as a first-passage time problem, where an event is triggered when the level of a protein crosses a critical threshold for the first time. Analytical calculations are performed for the first-passage time distribution in stochastic models of gene expression...
January 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28038456/dna-methylation-landscape-of-hepatoblastomas-reveals-arrest-at-early-stages-of-liver-differentiation-and-cancer-related-alterations
#14
Mariana Maschietto, Tatiane Cristina Rodrigues, André Yoshiaki Kashiwabara, Érica Sara Souza de Araujo, Talita Ferreira Marques Aguiar, Cecilia Maria Lima da Costa, Isabela Werneck da Cunha, Luciana Dos Reis Vasques, Monica Cypriano, Helena Brentani, Silvia Regina Caminada de Toledo, Peter Lees Pearson, Dirce Maria Carraro, Carla Rosenberg, Ana Cristina Victorino Krepischi
Hepatoblastomas are uncommon embryonal liver tumors accounting for approximately 80% of childhood hepatic cancer. We hypothesized that epigenetic changes, including DNA methylation, could be relevant to hepatoblastoma onset. The methylomes of eight matched hepatoblastomas and non-tumoral liver tissues were characterized, and data were validated in an independent group (11 hepatoblastomas). In comparison to differentiated livers, hepatoblastomas exhibited a widespread and non-stochastic pattern of global low-level hypomethylation...
December 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27997556/self-organizing-global-gene-expression-regulated-through-criticality-mechanism-of-the-cell-fate-change
#15
Masa Tsuchiya, Alessandro Giuliani, Midori Hashimoto, Jekaterina Erenpreisa, Kenichi Yoshikawa
BACKGROUND: A fundamental issue in bioscience is to understand the mechanism that underlies the dynamic control of genome-wide expression through the complex temporal-spatial self-organization of the genome to regulate the change in cell fate. We address this issue by elucidating a physically motivated mechanism of self-organization. PRINCIPAL FINDINGS: Building upon transcriptome experimental data for seven distinct cell fates, including early embryonic development, we demonstrate that self-organized criticality (SOC) plays an essential role in the dynamic control of global gene expression regulation at both the population and single-cell levels...
2016: PloS One
https://www.readbyqxmd.com/read/27983596/estrogenic-endocrine-disrupting-chemicals-influencing-nrf1-regulated-gene-networks-in-the-development-of-complex-human-brain-diseases
#16
REVIEW
Mark Preciados, Changwon Yoo, Deodutta Roy
During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs) because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA), polychlorinated biphenyls (PCBs), phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese...
December 13, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27977665/hierarchical-post-transcriptional-regulation-of-colicin-e2-expression-in-escherichia-coli
#17
Matthias Lechner, Mathias Schwarz, Madeleine Opitz, Erwin Frey
Post-transcriptional regulation of gene expression plays a crucial role in many bacterial pathways. In particular, the translation of mRNA can be regulated by trans-acting, small, non-coding RNAs (sRNAs) or mRNA-binding proteins, each of which has been successfully treated theoretically using two-component models. An important system that includes a combination of these modes of post-transcriptional regulation is the Colicin E2 system. DNA damage, by triggering the SOS response, leads to the heterogeneous expression of the Colicin E2 operon including the cea gene encoding the toxin colicin E2, and the cel gene that codes for the induction of cell lysis and release of colicin...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27919068/capturing-pairwise-and-multi-way-chromosomal-conformations-using-chromosomal-walks
#18
Pedro Olivares-Chauvet, Zohar Mukamel, Aviezer Lifshitz, Omer Schwartzman, Noa Oded Elkayam, Yaniv Lubling, Gintaras Deikus, Robert P Sebra, Amos Tanay
Chromosomes are folded into highly compacted structures to accommodate physical constraints within nuclei and to regulate access to genomic information. Recently, global mapping of pairwise contacts showed that loops anchoring topological domains (TADs) are highly conserved between cell types and species. Whether pairwise loops synergize to form higher-order structures is still unclear. Here we develop a conformation capture assay to study higher-order organization using chromosomal walks (C-walks) that link multiple genomic loci together into proximity chains in human and mouse cells...
December 8, 2016: Nature
https://www.readbyqxmd.com/read/27911801/mechanical-bounds-to-transcriptional-noise
#19
Stuart A Sevier, David A Kessler, Herbert Levine
Over the past several decades it has been increasingly recognized that stochastic processes play a central role in transcription. Although many stochastic effects have been explained, the source of transcriptional bursting (one of the most well-known sources of stochasticity) has continued to evade understanding. Recent results have pointed to mechanical feedback as the source of transcriptional bursting, but a reconciliation of this perspective with preexisting views of transcriptional regulation is lacking...
December 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27893965/single-cell-and-single-molecule-analysis-of-gene-expression-regulation
#20
Maria Vera, Jeetayu Biswas, Adrien Senecal, Robert H Singer, Hye Yoon Park
Recent advancements in single-cell and single-molecule imaging technologies have resolved biological processes in time and space that are fundamental to understanding the regulation of gene expression. Observations of single-molecule events in their cellular context have revealed highly dynamic aspects of transcriptional and post-transcriptional control in eukaryotic cells. This approach can relate transcription with mRNA abundance and lifetimes. Another key aspect of single-cell analysis is the cell-to-cell variability among populations of cells...
November 23, 2016: Annual Review of Genetics
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