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Stochastic gene regulation

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https://www.readbyqxmd.com/read/29451874/a-stochastic-and-dynamical-view-of-pluripotency-in-mouse-embryonic-stem-cells
#1
Yen Ting Lin, Peter G Hufton, Esther J Lee, Davit A Potoyan
Pluripotent embryonic stem cells are of paramount importance for biomedical sciences because of their innate ability for self-renewal and differentiation into all major cell lines. The fateful decision to exit or remain in the pluripotent state is regulated by complex genetic regulatory networks. The rapid growth of single-cell sequencing data has greatly stimulated applications of statistical and machine learning methods for inferring topologies of pluripotency regulating genetic networks. The inferred network topologies, however, often only encode Boolean information while remaining silent about the roles of dynamics and molecular stochasticity inherent in gene expression...
February 16, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29440659/the-effects-of-death-and-post-mortem-cold-ischemia-on-human-tissue-transcriptomes
#2
Pedro G Ferreira, Manuel Muñoz-Aguirre, Ferran Reverter, Caio P Sá Godinho, Abel Sousa, Alicia Amadoz, Reza Sodaei, Marta R Hidalgo, Dmitri Pervouchine, Jose Carbonell-Caballero, Ramil Nurtdinov, Alessandra Breschi, Raziel Amador, Patrícia Oliveira, Cankut Çubuk, João Curado, François Aguet, Carla Oliveira, Joaquin Dopazo, Michael Sammeth, Kristin G Ardlie, Roderic Guigó
Post-mortem tissues samples are a key resource for investigating patterns of gene expression. However, the processes triggered by death and the post-mortem interval (PMI) can significantly alter physiologically normal RNA levels. We investigate the impact of PMI on gene expression using data from multiple tissues of post-mortem donors obtained from the GTEx project. We find that many genes change expression over relatively short PMIs in a tissue-specific manner, but this potentially confounding effect in a biological analysis can be minimized by taking into account appropriate covariates...
February 13, 2018: Nature Communications
https://www.readbyqxmd.com/read/29438699/dna-methylation-patterns-separate-senescence-from-transformation-potential-and-indicate-cancer-risk
#3
Wenbing Xie, Ioannis Kagiampakis, Lixia Pan, Yang W Zhang, Lauren Murphy, Yong Tao, Xiangqian Kong, Byunghak Kang, Limin Xia, Filipe L F Carvalho, Subhojit Sen, Ray-Whay Chiu Yen, Cynthia A Zahnow, Nita Ahuja, Stephen B Baylin, Hariharan Easwaran
Overall shared DNA methylation patterns between senescence (Sen) and cancers have led to the model that tumor-promoting epigenetic patterns arise through senescence. We show that transformation-associated methylation changes arise stochastically and independently of programmatic changes during senescence. Promoter hypermethylation events in transformation involve primarily pro-survival and developmental genes, similarly modified in primary tumors. Senescence-associated hypermethylation mainly involves metabolic regulators and appears early in proliferating "near-senescent" cells, which can be immortalized but are refractory to transformation...
February 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29396410/discordant-congenital-zika-syndrome-twins-show-differential-in-vitro-viral-susceptibility-of-neural-progenitor-cells
#4
Luiz Carlos Caires-Júnior, Ernesto Goulart, Uirá Souto Melo, Bruno Silva Henrique Araujo, Lucas Alvizi, Alessandra Soares-Schanoski, Danyllo Felipe de Oliveira, Gerson Shigeru Kobayashi, Karina Griesi-Oliveira, Camila Manso Musso, Murilo Sena Amaral, Lucas Ferreira daSilva, Renato Mancini Astray, Sandra Fernanda Suárez-Patiño, Daniella Cristina Ventini, Sérgio Gomes da Silva, Guilherme Lopes Yamamoto, Suzana Ezquina, Michel Satya Naslavsky, Kayque Alves Telles-Silva, Karina Weinmann, Vanessa van der Linden, Helio van der Linden, João Mendes Ricardo de Oliveira, Nivia Rodrigues Maria Arrais, Adriana Melo, Thalita Figueiredo, Silvana Santos, Joanna Castro Goes Meira, Saulo Duarte Passos, Roque Pacheco de Almeida, Ana Jovina Barreto Bispo, Esper Abrão Cavalheiro, Jorge Kalil, Edécio Cunha-Neto, Helder Nakaya, Robert Andreata-Santos, Luis Carlos de Souza Ferreira, Sergio Verjovski-Almeida, Paulo Lee Ho, Maria Rita Passos-Bueno, Mayana Zatz
Congenital Zika syndrome (CZS) causes early brain development impairment by affecting neural progenitor cells (NPCs). Here, we analyze NPCs from three pairs of dizygotic twins discordant for CZS. We compare by RNA-Seq the NPCs derived from CZS-affected and CZS-unaffected twins. Prior to Zika virus (ZIKV) infection the NPCs from CZS babies show a significantly different gene expression signature of mTOR and Wnt pathway regulators, key to a neurodevelopmental program. Following ZIKV in vitro infection, cells from affected individuals have significantly higher ZIKV replication and reduced cell growth...
February 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29390613/likelihood-for-transcriptions-in-a-genetic-regulatory-system-under-asymmetric-stable-l%C3%A3-vy-noise
#5
Hui Wang, Xiujun Cheng, Jinqiao Duan, Jürgen Kurths, Xiaofan Li
This work is devoted to investigating the evolution of concentration in a genetic regulation system, when the synthesis reaction rate is under additive and multiplicative asymmetric stable Lévy fluctuations. By focusing on the impact of skewness (i.e., non-symmetry) in the probability distributions of noise, we find that via examining the mean first exit time (MFET) and the first escape probability (FEP), the asymmetric fluctuations, interacting with nonlinearity in the system, lead to peculiar likelihood for transcription...
January 2018: Chaos
https://www.readbyqxmd.com/read/29386401/efficient-analysis-of-stochastic-gene-dynamics-in-the-non-adiabatic-regime-using-piecewise-deterministic-markov-processes
#6
Yen Ting Lin, Nicolas E Buchler
Single-cell experiments show that gene expression is stochastic and bursty, a feature that can emerge from slow switching between promoter states with different activities. In addition to slow chromatin and/or DNA looping dynamics, one source of long-lived promoter states is the slow binding and unbinding kinetics of transcription factors to promoters, i.e. the non-adiabatic binding regime. Here, we introduce a simple analytical framework, known as a piecewise deterministic Markov process (PDMP), that accurately describes the stochastic dynamics of gene expression in the non-adiabatic regime...
January 2018: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29378891/nutritional-regulation-of-the-sae-two-component-system-by-cody-in-staphylococcus-aureus
#7
Kevin D Mlynek, William E Sause, Derek E Moormeier, Marat R Sadykov, Kurt R Hill, Victor J Torres, Kenneth W Bayles, Shaun R Brinsmade
Staphylococcus aureus subverts innate defenses during infection in part by killing host immune cells to exacerbate disease. This human pathogen intercepts host cues and activates a transcriptional response via the S. aureus exoprotein expression (SaeR/S) two-component system to secrete virulence factors critical for pathogenesis. We recently showed that the transcriptional repressor CodY adjusts nuclease (nuc) gene expression via SaeR/S but the mechanism remained unknown. Herein, we identified two CodY binding motifs upstream of the sae P1 promoter, which suggested direct regulation by this global regulator...
January 29, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29366822/performance-limits-and-trade-offs-in-entropy-driven-biochemical-computers
#8
Dominique Chu
It is now widely accepted that biochemical reaction networks can perform computations. Examples are kinetic proof reading, gene regulation, or signalling networks. For many of these systems it was found that their computational performance is limited by a trade-off between the metabolic cost, the speed and the accuracy of the computation. In order to gain insight into the origins of these trade-offs, we consider entropy-driven computers as a model of biochemical computation. Using tools from stochastic thermodynamics, we show that entropy-driven computation is subject to a trade-off between accuracy and metabolic cost, but does not involve time-trade-offs...
January 20, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29347696/stochastic-dynamics-of-genetic-broadcasting-networks
#9
Davit A Potoyan, Peter G Wolynes
The complex genetic programs of eukaryotic cells are often regulated by key transcription factors occupying or clearing out of a large number of genomic locations. Orchestrating the residence times of these factors is therefore important for the well organized functioning of a large network. The classic models of genetic switches sidestep this timing issue by assuming the binding of transcription factors to be governed entirely by thermodynamic protein-DNA affinities. Here we show that relying on passive thermodynamics and random release times can lead to a "time-scale crisis" for master genes that broadcast their signals to a large number of binding sites...
November 2017: Physical Review. E
https://www.readbyqxmd.com/read/29343748/sac7-and-rho1-regulate-the-white-to-opaque-switching-in-candida-albicans
#10
Siwy Ling Yang, Guisheng Zeng, Fong Yee Chan, Yan-Ming Wang, Dongliang Yang, Yue Wang
Candida albicans cells homozygous at the mating-type locus stochastically undergo the white-to-opaque switching to become mating-competent. This switching is regulated by a core circuit of transcription factors organized through interlocking feedback loops around the master regulator Wor1. Although a range of distinct environmental cues is known to induce the switching, the pathways linking the external stimuli to the central control mechanism remains largely unknown. By screening a C. albicans haploid gene-deletion library, we found that SAC7 encoding a GTPase-activating protein of Rho1 is required for the white-to-opaque switching...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343631/stochastic-resonances-in-a-distributed-genetic-broadcasting-system-the-nf%C3%AE%C2%BAb-i%C3%AE%C2%BAb-paradigm
#11
Zhipeng Wang, Davit A Potoyan, Peter G Wolynes
Gene regulatory networks must relay information from extracellular signals to downstream genes in an efficient, timely and coherent manner. Many complex functional tasks such as the immune response require system-wide broadcasting of information not to one but to many genes carrying out distinct functions whose dynamical binding and unbinding characteristics are widely distributed. In such broadcasting networks, the intended target sites are also often dwarfed in number by the even more numerous non-functional binding sites...
January 2018: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29323382/probing-transcription-factor-binding-activity-and-downstream-gene-silencing-in-living-cells-with-a-dna-nanoswitch
#12
Alessandro Bertucci, Junling Guo, Nicolas Oppmann, Agata Glab, Francesco Ricci, Frank Caruso, Francesca Cavalieri
Transcription factor DNA binding activity is of pivotal importance in living systems because of its primary involvement in the regulation of genetic machinery. The analysis of transient expression levels of transcription factors in response to a certain cell status is a powerful means for investigating cellular dynamics at the biomolecular level. Herein, a DNA-based molecular switch that enables probing of transcription factor DNA binding activity is directly used in living cells. We demonstrate that the DNA nanoswitch allows for dynamic fluorescence imaging of NF-κB and quantification of downstream gene silencing in real time...
January 11, 2018: Nanoscale
https://www.readbyqxmd.com/read/29321537/computational-investigation-of-environment-noise-interaction-in-single-cell-organisms-the-merit-of-expression-stochasticity-depends-on-the-quality-of-environmental-fluctuations
#13
Anja Lück, Lukas Klimmasch, Peter Großmann, Sebastian Germerodt, Christoph Kaleta
Organisms need to adapt to changing environments and they do so by using a broad spectrum of strategies. These strategies include finding the right balance between expressing genes before or when they are needed, and adjusting the degree of noise inherent in gene expression. We investigated the interplay between different nutritional environments and the inhabiting organisms' metabolic and genetic adaptations by applying an evolutionary algorithm to an agent-based model of a concise bacterial metabolism. Our results show that constant environments and rapidly fluctuating environments produce similar adaptations in the organisms, making the predictability of the environment a major factor in determining optimal adaptation...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29317513/cyclic-amp-regulates-bacterial-persistence-through-repression-of-the-oxidative-stress-response-and-sos-dependent-dna-repair-in-uropathogenic-escherichia-coli
#14
Roberto C Molina-Quiroz, Cecilia Silva-Valenzuela, Jennifer Brewster, Eduardo Castro-Nallar, Stuart B Levy, Andrew Camilli
Bacterial persistence is a transient, nonheritable physiological state that provides tolerance to bactericidal antibiotics. The stringent response, toxin-antitoxin modules, and stochastic processes, among other mechanisms, play roles in this phenomenon. How persistence is regulated is relatively ill defined. Here we show that cyclic AMP, a global regulator of carbon catabolism and other core processes, is a negative regulator of bacterial persistence in uropathogenic Escherichia coli, as measured by survival after exposure to a β-lactam antibiotic...
January 9, 2018: MBio
https://www.readbyqxmd.com/read/29305013/transcription-insights-from-the-hiv-1-promoter
#15
Enrico Ne, Robert-Jan Palstra, Tokameh Mahmoudi
In this review, we cover transcription regulation of human immunodeficiency virus type 1 (HIV-1) gene expression, focusing on the invaluable contributions, made by HIV research over the years, toward the field of transcription. In this context, the HIV promoter can be considered to be a well-studied model promoter, which although a viral promoter, is subject to the same cellular regulatory mechanisms that modulate the transcriptional control of endogenous host cellular genes. The molecular control of HIV-1 transcription has been well studied and considerable knowledge toward development of alternative strategies for therapies aimed at eradicating both active but also latent HIV-1 has been obtained...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29247011/histone-demethylase-activity-of-utx-is-essential-for-viability-and-regulation-of%C3%A2-hox-gene-expression-in%C3%A2-drosophila
#16
Ömer Copur, Jürg Müller
The trimethylation of histone H3 at lysine 27 (H3K27me3) by Polycomb Repressive Complex 2 (PRC2) is essential for repression of Polycomb target genes. The role of enzymatic demethylation of H3K27me3 by the KDM6-family demethylases Utx, Uty and JmjD3 is however less clear. Studies in both mice and worms led to the proposal that KDM6 proteins but not their H3K27me3 demethylase activity is critical for normal development. Here, we investigated the requirement of the demethylase activity of the single KDM6 family member Utx in Drosophila We generated Drosophila expressing full-length but catalytic inactive Utx protein and found that these mutants show the same phenotypes like animals lacking Utx protein...
December 15, 2017: Genetics
https://www.readbyqxmd.com/read/29242386/dosage-dependent-expression-variation-suppressed-on-the-drosophila-male-x-chromosome
#17
Hangnoh Lee, Dong-Yeon Cho, Damian Wojtowicz, Susan T Harbison, Steven Russell, Brian Oliver, Teresa Przytycka
DNA copy number variation is associated with many high phenotypic heterogeneity disorders. We systematically examined the impact of Drosophila melanogaster deletions on gene expression profiles to ask if increased expression variability due to reduced gene dose might underlie this phenotypic heterogeneity. Indeed, we find that one dose genes have higher gene expression variability relative to two dose genes. We then asked if this increase in variability could be explained by intrinsic noise within cells, due to stochastic biochemical events, or if expression variability is due to extrinsic noise arising from more complex interactions...
December 13, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29228658/dna-methylation-landscape-of-hepatoblastomas-reveals-arrest-at-early-stages-of-liver-differentiation-and-cancer-related-alterations
#18
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 C V 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...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29218900/single-subject-transcriptome-analysis-to-identify-functionally-signed-gene-set-or-pathway-activity
#19
Joanne Berghout, Qike Li, Nima Pouladi, Jianrong Li, Yves A Lussier
Analysis of single-subject transcriptome response data is an unmet need of precision medicine, made challenging by the high dimension, dynamic nature and difficulty in extracting meaningful signals from biological or stochastic noise. We have proposed a method for single subject analysis that uses a mixture model for transcript fold-change clustering from isogenically paired samples, followed by integration of these distributions with Gene Ontology Biological Processes (GO-BP) to reduce dimension and identify functional attributes...
2018: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/29177465/aminoglycoside-mediated-promotion-of-translation-readthrough-occurs-through-a-non-stochastic-mechanism-that-competes-with-translation-termination
#20
H M Chowdhury, M A Siddiqui, S Kanneganti, N Sharmin, M W Chowdhury, Talat Nasim
Attempts have been made to treat nonsense-associated genetic disorders by chemical agents and hence an improved mechanistic insight into the decoding of readthrough signals is essential for the identification and characterisation of factors for the treatment of these disorders. To identify either novel compounds or genes that modulate translation readthrough, we have employed dual reporter-based high-throughput screens that use enzymatic and fluorescence activities and screened bio-active NINDS compounds (n = 1000) and siRNA (n = 288) libraries...
November 21, 2017: Human Molecular Genetics
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