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Stochastic gene regulation

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https://www.readbyqxmd.com/read/27893965/single-cell-and-single-molecule-analysis-of-gene-expression-regulation
#1
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
https://www.readbyqxmd.com/read/27893768/macromolecular-crowding-regulates-the-gene-expression-profile-by-limiting-diffusion
#2
Mahdi Golkaram, Stefan Hellander, Brian Drawert, Linda R Petzold
We seek to elucidate the role of macromolecular crowding in transcription and translation. It is well known that stochasticity in gene expression can lead to differential gene expression and heterogeneity in a cell population. Recent experimental observations by Tan et al. have improved our understanding of the functional role of macromolecular crowding. It can be inferred from their observations that macromolecular crowding can lead to robustness in gene expression, resulting in a more homogeneous cell population...
November 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27875323/estimating-intrinsic-and-extrinsic-noise-from-single-cell-gene-expression-measurements
#3
Audrey Qiuyan Fu, Lior Pachter
Gene expression is stochastic and displays variation ("noise") both within and between cells. Intracellular (intrinsic) variance can be distinguished from extracellular (extrinsic) variance by applying the law of total variance to data from two-reporter assays that probe expression of identically regulated gene pairs in single cells. We examine established formulas [Elowitz, M. B., A. J. Levine, E. D. Siggia and P. S. Swain (2002): "Stochastic gene expression in a single cell," Science, 297, 1183-1186.] for the estimation of intrinsic and extrinsic noise and provide interpretations of them in terms of a hierarchical model...
December 1, 2016: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/27858532/tracking-the-evolution-of-epialleles-during-neural-differentiation-and-brain-development-d-aspartate-oxidase-as-a-model-gene
#4
Ermanno Florio, Simona Keller, Lorena Coretti, Ornella Affinito, Giovanni Scala, Francesco Errico, Annalisa Fico, Francesca Boscia, Maria Josè Sisalli, Mafalda Giovanna Reccia, Gennaro Miele, Antonella Monticelli, Antonella Scorziello, Francesca Lembo, Luca Colucci-D'Amato, Gabriella Minchiotti, Vittorio Enrico Avvedimento, Alessandro Usiello, Sergio Cocozza, Lorenzo Chiariotti
We performed ultra-deep methylation analysis at single molecule level of the promoter region of developmentally regulated D-Aspartate oxidase (Ddo), as a model gene, during brain development and embryonic stem cell neural differentiation. Single molecule methylation analysis enabled us to establish the effective epiallele composition within mixed or pure brain cell populations. In this framework, an epiallele is defined as a specific combination of methylated CpG within Ddo locus and can represent the epigenetic haplotype revealing a cell-to-cell methylation heterogeneity...
November 18, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27835978/importins-promote-high-frequency-nf-%C3%AE%C2%BAb-oscillations-increasing-information-channel-capacity
#5
Zbigniew Korwek, Karolina Tudelska, Paweł Nałęcz-Jawecki, Maciej Czerkies, Wiktor Prus, Joanna Markiewicz, Marek Kochańczyk, Tomasz Lipniacki
BACKGROUND: Importins and exportins influence gene expression by enabling nucleocytoplasmic shuttling of transcription factors. A key transcription factor of innate immunity, NF-κB, is sequestered in the cytoplasm by its inhibitor, IκBα, which masks nuclear localization sequence of NF-κB. In response to TNFα or LPS, IκBα is degraded, which allows importins to bind NF-κB and shepherd it across nuclear pores. NF-κB nuclear activity is terminated when newly synthesized IκBα enters the nucleus, binds NF-κB and exportin which directs the complex to the cytoplasm...
November 11, 2016: Biology Direct
https://www.readbyqxmd.com/read/27835699/gasdermin-c-is-upregulated-by-inactivation-of-transforming-growth-factor-%C3%AE-receptor-type-ii-in-the-presence-of-mutated-apc-promoting-colorectal-cancer-proliferation
#6
Masashi Miguchi, Takao Hinoi, Manabu Shimomura, Tomohiro Adachi, Yasufumi Saito, Hiroaki Niitsu, Masatoshi Kochi, Haruki Sada, Yusuke Sotomaru, Tsuneo Ikenoue, Kunitoshi Shigeyasu, Kohji Tanakaya, Yasuhiko Kitadai, Kazuhiro Sentani, Naohide Oue, Wataru Yasui, Hideki Ohdan
Mutations in TGFBR2, a component of the transforming growth factor (TGF)-β signaling pathway, occur in high-frequency microsatellite instability (MSI-H) colorectal cancer (CRC). In mouse models, Tgfbr2 inactivation in the intestinal epithelium accelerates the development of malignant intestinal tumors in combination with disruption of the Wnt-β-catenin pathway. However, no studies have further identified the genes influenced by TGFBR2 inactivation following disruption of the Wnt-β-catenin pathway. We previously described CDX2P-G19Cre;Apcflox/flox mice, which is stochastically null for Apc in the colon epithelium...
2016: PloS One
https://www.readbyqxmd.com/read/27832998/mathematical-aspects-of-the-regulation-of-gene-transcription-by-promoters
#7
Vladimir P Zhdanov
Although the transcriptional regulation of gene expression has been a subject of intense experimental and theoretical studies over the past several decades, the understanding of this process is still incomplete. In particular, the models focused on the function of transcription factors usually take into account only the lateral interactions between them in the ground bound state. The rates of attachment and detachment of transcription factors on the promoter sites depend, however, also on the lateral interactions in the activated state...
November 8, 2016: Mathematical Biosciences
https://www.readbyqxmd.com/read/27773987/how-genes-modulate-patterns-of-aging-related-changes-on-the-way-to-100-biodemographic-models-and-methods-in-genetic-analyses-of-longitudinal-data
#8
Anatoliy I Yashin, Konstantin G Arbeev, Deqing Wu, Liubov Arbeeva, Alexander Kulminski, Irina Kulminskaya, Igor Akushevich, Svetlana V Ukraintseva
BACKGROUND AND OBJECTIVE: To clarify mechanisms of genetic regulation of human aging and longevity traits, a number of genome-wide association studies (GWAS) of these traits have been performed. However, the results of these analyses did not meet expectations of the researchers. Most detected genetic associations have not reached a genome-wide level of statistical significance, and suffered from the lack of replication in the studies of independent populations. The reasons for slow progress in this research area include low efficiency of statistical methods used in data analyses, genetic heterogeneity of aging and longevity related traits, possibility of pleiotropic (e...
2016: North American Actuarial Journal: NAAJ
https://www.readbyqxmd.com/read/27771899/determining-the-roles-of-inositol-trisphosphate-receptors-in-neurodegeneration-interdisciplinary-perspectives-on-a-complex-topic
#9
Silvia Honda Takada, Juliane Midori Ikebara, Erica de Sousa, Débora Sterzeck Cardoso, Rodrigo Ribeiro Resende, Henning Ulrich, Martin Rückl, Sten Rüdiger, Alexandre Hiroaki Kihara
It is well known that calcium (Ca(2+)) is involved in the triggering of neuronal death. Ca(2+) cytosolic levels are regulated by Ca(2+) release from internal stores located in organelles, such as the endoplasmic reticulum. Indeed, Ca(2+) transit from distinct cell compartments follows complex dynamics that are mediated by specific receptors, notably inositol trisphosphate receptors (IP3Rs). Ca(2+) release by IP3Rs plays essential roles in several neurological disorders; however, details of these processes are poorly understood...
October 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27711197/a-multistate-toggle-switch-defines-fungal-cell-fates-and-is-regulated-by-synergistic-genetic-cues
#10
Matthew Z Anderson, Allison M Porman, Na Wang, Eugenio Mancera, Denis Huang, Christina A Cuomo, Richard J Bennett
Heritable epigenetic changes underlie the ability of cells to differentiate into distinct cell types. Here, we demonstrate that the fungal pathogen Candida tropicalis exhibits multipotency, undergoing stochastic and reversible switching between three cellular states. The three cell states exhibit unique cellular morphologies, growth rates, and global gene expression profiles. Genetic analysis identified six transcription factors that play key roles in regulating cell differentiation. In particular, we show that forced expression of Wor1 or Efg1 transcription factors can be used to manipulate transitions between all three cell states...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27672159/hypothesis-type-i-toxin-antitoxin-genes-enter-the-persistence-field-a-feedback-mechanism-explaining-membrane-homoeostasis
#11
REVIEW
Kenn Gerdes
Bacteria form persisters, cells that are tolerant to multiple antibiotics and other types of environmental stress. Persister formation can be induced either stochastically in single cells of a growing bacterial ensemble, or by environmental stresses, such as nutrient starvation, in a subpopulation of cells. In many cases, the molecular mechanisms underlying persistence are still unknown. However, there is growing evidence that, in enterobacteria, both stochastically and environmentally induced persistence are controlled by the second messenger (p)ppGpp...
November 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/27665109/gene-expression-noise-is-affected-differentially-by-feedback-in-burst-frequency-and-burst-size
#12
Pavol Bokes, Abhyudai Singh
Inside individual cells, expression of genes is stochastic across organisms ranging from bacterial to human cells. A ubiquitous feature of stochastic expression is burst-like synthesis of gene products, which drives considerable intercellular variability in protein levels across an isogenic cell population. One common mechanism by which cells control such stochasticity is negative feedback regulation, where a protein inhibits its own synthesis. For a single gene that is expressed in bursts, negative feedback can affect the burst frequency or the burst size...
September 24, 2016: Journal of Mathematical Biology
https://www.readbyqxmd.com/read/27658712/the-molecular-choreography-of-protein-synthesis-translational-control-regulation-and-pathways
#13
Jin Chen, Junhong Choi, Seán E O'Leary, Arjun Prabhakar, Alexey Petrov, Rosslyn Grosely, Elisabetta Viani Puglisi, Joseph D Puglisi
Translation of proteins by the ribosome regulates gene expression, with recent results underscoring the importance of translational control. Misregulation of translation underlies many diseases, including cancer and many genetic diseases. Decades of biochemical and structural studies have delineated many of the mechanistic details in prokaryotic translation, and sketched the outlines of eukaryotic translation. However, translation may not proceed linearly through a single mechanistic pathway, but likely involves multiple pathways and branchpoints...
January 2016: Quarterly Reviews of Biophysics
https://www.readbyqxmd.com/read/27630669/a-comparison-of-deterministic-and-stochastic-modeling-approaches-for-biochemical-reaction-systems-on-fixed-points-means-and-modes
#14
Sayuri K Hahl, Andreas Kremling
In the mathematical modeling of biochemical reactions, a convenient standard approach is to use ordinary differential equations (ODEs) that follow the law of mass action. However, this deterministic ansatz is based on simplifications; in particular, it neglects noise, which is inherent to biological processes. In contrast, the stochasticity of reactions is captured in detail by the discrete chemical master equation (CME). Therefore, the CME is frequently applied to mesoscopic systems, where copy numbers of involved components are small and random fluctuations are thus significant...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27597760/visualization-of-single-endogenous-polysomes-reveals-the-dynamics-of-translation-in-live-human-cells
#15
Xavier Pichon, Amandine Bastide, Adham Safieddine, Racha Chouaib, Aubin Samacoits, Eugenia Basyuk, Marion Peter, Florian Mueller, Edouard Bertrand
Translation is an essential step in gene expression. In this study, we used an improved SunTag system to label nascent proteins and image translation of single messenger ribonucleoproteins (mRNPs) in human cells. Using a dedicated reporter RNA, we observe that translation of single mRNPs stochastically turns on and off while they diffuse through the cytoplasm. We further measure a ribosome density of 1.3 per kilobase and an elongation rate of 13-18 amino acids per second. Tagging the endogenous POLR2A gene revealed similar elongation rates and ribosomal densities and that nearly all messenger RNAs (mRNAs) are engaged in translation...
September 12, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27589475/chromosome-5q33-deletions-associated-with-congenital-heart-defects
#16
Molly Starkovich, Seema R Lalani, Catherine L Mercer, Daryl A Scott
Congenital heart defects (CHD) are present in over 1% of all newborns and are the leading cause of birth-defect-related deaths in the United States. We describe two male subjects with CHD, one with an atrial septal defect, a ventricular septal defect, and pulmonary artery stenosis; and the other with tetralogy of Fallot and a right aortic arch, who carry partially overlapping, de novo deletions of chromosome 5q33. The maximum region of overlap between these deletions encompasses HAND1 and SAP30L, two genes that have previously been shown to play a role in cardiac development...
September 2, 2016: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/27582426/defining-distinguishing-and-detecting-the-contribution-of-heterogeneous-methylation-to-cancer-heterogeneity
#17
Thomas R Pisanic, Pornpat Athamanolap, Tza-Huei Wang
DNA methylation is a fundamental means of epigenetic gene regulation that occurs in virtually all cell types. In many higher organisms, including humans, it plays vital roles in cell differentiation and homeostatic maintenance of cell phenotype. The control of DNA methylation has traditionally been attributed to a highly coordinated, linear process, whose dysregulation has been associated with numerous pathologies including cancer, where it occurs early in, and even prior to, the development of neoplastic tissues...
August 28, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27550220/congenital-heart-defects-and-left-ventricular-non-compaction-in-males-with-loss-of-function-variants-in-nono
#18
Daryl A Scott, Andres Hernandez-Garcia, Mahshid S Azamian, Valerie K Jordan, Bum Jun Kim, Molly Starkovich, Jinglan Zhang, Lee-Jun Wong, Sandra A Darilek, Amy M Breman, Yaping Yang, James R Lupski, Amyn K Jiwani, Bibhuti Das, Seema R Lalani, Alejandro D Iglesias, Jill A Rosenfeld, Fan Xia
BACKGROUND: The non-POU domain containing octamer-binding gene (NONO) is located on chromosome Xq13.1 and encodes a member of a small family of RNA-binding and DNA-binding proteins that perform a variety of tasks involved in RNA synthesis, transcriptional regulation and DNA repair. Loss-of-function variants in NONO have been described as a cause of intellectual disability in males but have not been described in association with congenital heart defects or cardiomyopathy. In this article, we seek to further define the phenotypic consequences of NONO depletion in human subjects...
August 22, 2016: Journal of Medical Genetics
https://www.readbyqxmd.com/read/27534795/symplasmata-are-a-clonal-conditional-and-reversible-type-of-bacterial-multicellularity
#19
Robin Tecon, Johan H J Leveau
Microorganisms are capable of remarkable social behaviours, such as forming transient multicellular assemblages with properties and adaptive abilities exceeding those of individual cells. Here, we report on the formation and structure of genets known as symplasmata produced by Pantoea eucalypti bacteria. Each symplasmatum develops clonally and stochastically from a single bacterium into a membrane-delimited, capsule-embedded cluster of progeny cells and with a frequency that depends on temperature, pH, and nutrient availability...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27528448/influence-of-gene-copy-number-on-self-regulated-gene-expression
#20
Jakub Jędrak, Anna Ochab-Marcinek
Using an analytically solvable stochastic model, we study the properties of a simple genetic circuit consisting of multiple copies of a self-regulating gene. We analyse how the variation in gene copy number and the mutations changing the auto-regulation strength affect the steady-state distribution of protein concentration. We predict that one-reporter assay, an experimental method where the extrinsic noise level is inferred from the comparison of expression variance of a single and duplicated reporter gene, may give an incorrect estimation of the extrinsic noise contribution when applied to self-regulating genes...
November 7, 2016: Journal of Theoretical Biology
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