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https://www.readbyqxmd.com/read/28809965/hill-kinetics-as-a-noise-filter-the-role-of-transcription-factor-autoregulation-in-gene-cascades
#1
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 15, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28802080/segmental-allotetraploidy-generates-extensive-homeologous-expression-rewiring-and-phenotypic-diversity-at-the-population-level-in-rice
#2
Yue Sun, Ying Wu, Chunwu Yang, Shuai Sun, Xiuyun Lin, Lixia Liu, Chunming Xu, Jonathan F Wendel, Lei Gong, Bao Liu
Allopolyploidization, i.e., concomitant merging and doubling of two or more divergent genomes in a common nucleus/cytoplasm, is known to instantly alter genome-wide transcriptome dynamics, a phenomenon referred to as "transcriptomic shock". However, the immediate effects of transcriptomic alteration in generating phenotypic diversity at the population level remain under-investigated. Here, we employed the MassARRAY-based Sequenom platform to assess and compare orthologous, allelic, and homeologous gene expression status in two tissues (leaf and root) of a set of randomly chosen individuals from populations of parental rice subspecies (indica and japonica), in vitro "hybrids" (parental mixes), reciprocal F1 hybrids and reciprocal tetraploids at the 5(th) -selfed generation (S5)...
August 12, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28799233/stochastics-of-cellular-differentiation-explained-by-epigenetics-the-case-of-t-cell-differentiation-and-functional-plasticity
#3
REVIEW
Jaydeep Bhat, Johannes Helmuth, Guranda Chitadze, Léonce Kouakanou, Christian Peters, Martin Vingron, Ole Ammerpohl, Dieter Kabelitz
Epigenetic marks including histone modifications and DNA methylation are associated to 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...
August 10, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28796841/single-cell-qpcr-reveals-that-additional-hand2-and-microrna-1-facilitate-the-early-reprogramming-progress-of-seven-factor-induced-human-myocytes
#4
Emre Bektik, Adrienne Dennis, Prateek Prasanna, Anant Madabhushi, Ji-Dong Fu
The direct reprogramming of cardiac fibroblasts into induced cardiomyocyte (CM)-like cells (iCMs) holds great promise in restoring heart function. We previously found that human fibroblasts could be reprogrammed toward CM-like cells by 7 reprogramming factors; however, iCM reprogramming in human fibroblasts is both more difficult and more time-intensive than that in mouse cells. In this study, we investigated if additional reprogramming factors could quantitatively and/or qualitatively improve 7-factor-mediated human iCM reprogramming by single-cell quantitative PCR...
2017: PloS One
https://www.readbyqxmd.com/read/28794219/dodging-silver-bullets-good-crispr-gene-drive-design-is-critical-for-eradicating-exotic-vertebrates
#5
Thomas A A Prowse, Phillip Cassey, Joshua V Ross, Chandran Pfitzner, Talia A Wittmann, Paul Thomas
Self-replicating gene drives that can spread deleterious alleles through animal populations have been promoted as a much needed but controversial 'silver bullet' for controlling invasive alien species. Homing-based drives comprise an endonuclease and a guide RNA (gRNA) that are replicated during meiosis via homologous recombination. However, their efficacy for controlling wild populations is threatened by inherent polymorphic resistance and the creation of resistance alleles via non-homologous end-joining (NHEJ)-mediated DNA repair...
August 16, 2017: Proceedings. Biological Sciences
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
#6
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/28781712/trom-a-testing-based-method-for-finding-transcriptomic-similarity-of-biological-samples
#7
Wei Vivian Li, Yiling Chen, Jingyi Jessica Li
Comparative transcriptomics has gained increasing popularity in genomic research thanks to the development of high-throughput technologies including microarray and next-generation RNA sequencing that have generated numerous transcriptomic data. An important question is to understand the conservation and divergence of biological processes in different species. We propose a testing-based method TROM (Transcriptome Overlap Measure) for comparing transcriptomes within or between different species, and provide a different perspective, in contrast to traditional correlation analyses, about capturing transcriptomic similarity...
June 2017: Statistics in Biosciences
https://www.readbyqxmd.com/read/28768640/clonal-expansion-and-interrelatedness-of-distinct-b-lineage-compartments-in-multiple-myeloma-bone-marrow
#8
Leo Hansmann, Arnold Han, Livius Penter, Michaela Liedtke, Mark M Davis
Multiple myeloma is characterized by the clonal expansion of malignant plasma cells in the bone marrow. But the phenotypic diversity and the contribution of less predominant B-lineage clones to the biology of this disease have been controversial. Here we asked whether cells bearing the dominant multiple myeloma immunoglobulin rearrangement occupy phenotypic compartments other than that of plasma cells. To accomplish this, we combined 13-parameter FACS index sorting and t-Stochastic Neighbor Embedding (t-SNE) visualization with high-throughput single-cell immunoglobulin sequencing to track selected B-lineage clones across different stages of human B-cell development...
August 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28765980/the-aboveground-vegetation-type-and-underground-soil-property-mediate-the-divergence-of-soil-microbiomes-and-the-biological-interactions
#9
Shu-Hong Wu, Bing-Hong Huang, Chia-Lung Huang, Gang Li, Pei-Chun Liao
The composition of the soil microbiome is influenced by environmental (abiotic) variables and biological interactions (biotic factors). To determine whether the aboveground vegetation and soil physicochemical properties were the main determinant of beta-diversity and biological interaction of soil microbial community, we sampled soils from the temperate coniferous forest and grassland. Clustering of operational taxonomic units was conducted using 16S rRNA gene. We found that the microbial composition of the rhizospheres, in which root exudates influence the microbial environment, show lower alpha-diversity than that of nonroot soils...
August 1, 2017: Microbial Ecology
https://www.readbyqxmd.com/read/28754144/a-novel-mechanism-for-variable-phenotypic-expressivity-in-mendelian-diseases-uncovered-by-an-au-rich-element-are-creating-mutation
#10
Nisha Patel, Arif O Khan, Maher Al-Saif, Walid N Moghrabi, Balsam M AlMaarik, Niema Ibrahim, Firdous Abdulwahab, Mais Hashem, Tarfa Alshidi, Eman Alobeid, Rana A Alomar, Saad Al-Harbi, Mohamed Abouelhoda, Khalid S A Khabar, Fowzan S Alkuraya
BACKGROUND: Variable expressivity is a well-known phenomenon in which patients with mutations in one gene display varying degrees of clinical severity, potentially displaying only subsets of the clinical manifestations associated with the multisystem disorder linked to the gene. This remains an incompletely understood phenomenon with proposed mechanisms ranging from allele-specific to stochastic. RESULTS: We report three consanguineous families in which an isolated ocular phenotype is linked to a novel 3' UTR mutation in SLC4A4, a gene known to be mutated in a syndromic form of intellectual disability with renal and ocular involvement...
July 28, 2017: Genome Biology
https://www.readbyqxmd.com/read/28741470/ecological-feedback-in-quorum-sensing-microbial-populations-can-induce-heterogeneous-production-of-autoinducers
#11
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/28740089/effects-of-growth-rate-and-promoter-activity-on-single-cell-protein-expression
#12
Niclas Nordholt, Johan van Heerden, Remco Kort, Frank J Bruggeman
Protein expression in a single cell depends on its global physiological state. Moreover, genetically-identical cells exhibit variability (noise) in protein expression, arising from the stochastic nature of biochemical processes, cell growth and division. While it is well understood how cellular growth rate influences mean protein expression, little is known about the relationship between growth rate and noise in protein expression. Here we quantify this relationship in Bacillus subtilis by a novel combination of experiments and theory...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729840/cardiac-subtype-specific-modeling-of-kv1-5-ion-channel-deficiency-using-human-pluripotent-stem-cells
#13
Maike Marczenke, Ilaria Piccini, Isabella Mengarelli, Jakob Fell, Albrecht Röpke, Guiscard Seebohm, Arie O Verkerk, Boris Greber
The ultrarapid delayed rectifier K(+) current (IKur), mediated by Kv1.5 channels, constitutes a key component of the atrial action potential. Functional mutations in the underlying KCNA5 gene have been shown to cause hereditary forms of atrial fibrillation (AF). Here, we combine targeted genetic engineering with cardiac subtype-specific differentiation of human induced pluripotent stem cells (hiPSCs) to explore the role of Kv1.5 in atrial hiPSC-cardiomyocytes. CRISPR/Cas9-mediated mutagenesis of integration-free hiPSCs was employed to generate a functional KCNA5 knockout...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28729483/epigenetic-plasticity-and-the-hallmarks-of-cancer
#14
REVIEW
William A Flavahan, Elizabeth Gaskell, Bradley E Bernstein
Chromatin and associated epigenetic mechanisms stabilize gene expression and cellular states while also facilitating appropriate responses to developmental or environmental cues. Genetic, environmental, or metabolic insults can induce overly restrictive or overly permissive epigenetic landscapes that contribute to pathogenesis of cancer and other diseases. Restrictive chromatin states may prevent appropriate induction of tumor suppressor programs or block differentiation. By contrast, permissive or "plastic" states may allow stochastic oncogene activation or nonphysiologic cell fate transitions...
July 21, 2017: Science
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
#15
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
#16
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...
July 18, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28716960/bacterial-tubulin-a-b-exhibit-polarized-growth-mixed-polarity-bundling-and-destabilization-by-gtp-hydrolysis
#17
César Díaz-Celis, Viviana I Risca, Felipe Hurtado, Jessica K Polka, Scott D Hansen, Daniel Maturana, Rosalba Lagos, R Dyche Mullins, Octavio Monasterio
Bacteria of the genus Prosthecobacter express homologs of eukaryotic α- and β-tubulin, called BtubA and BtubB, that have been observed to assemble into filaments in presence of GTP. BtubA/B polymers are proposed to be composed in vitro by two to six protofilaments, in contrast to in vivo where they have been reported to form 5-protofilaments tubes named bacterial microtubules (bMTs). The btubAB genes likely entered the Prosthecobacter lineage via horizontal gene transfer and may derive from an early ancestor of the modern eukaryotic microtubule (MT)...
July 17, 2017: Journal of Bacteriology
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/28714002/identification-of-key-genes-in-gram%C3%A2-positive-and-gram%C3%A2-negative-sepsis-using-stochastic-perturbation
#19
Zhenliang Li, Ying Zhang, Yaling Liu, Yanchun Liu, Youyi Li
Sepsis is an inflammatory response to pathogens (such as Gram‑positive and Gram‑negative bacteria), which has high morbidity and mortality in critically ill patients. The present study aimed to identify the key genes in Gram‑positive and Gram‑negative sepsis. GSE6535 was downloaded from Gene Expression Omnibus, containing 17 control samples, 18 Gram‑positive samples and 25 Gram‑negative samples. Subsequently, the limma package in R was used to screen the differentially expressed genes (DEGs). Hierarchical clustering was conducted for the specific DEGs in Gram‑negative and Gram‑negative samples using cluster software and the TreeView software...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28709943/propagation-and-control-of-gene-expression-noise-with-non-linear-translation-kinetics
#20
J David Van Dyken
Gene expression is a stochastic process involving small numbers of molecules. As a consequence, cells in a clonal population vary randomly and sometimes substantially from one another in the concentration of mRNA and protein species, a phenomenon known as gene expression noise. Previous theoretical models of gene expression noise assumed that translation is first-order (linear) in mRNA concentration, leading to unfiltered propagation of mRNA noise to the protein level. Here I consider the biological ramifications of relaxing this assumption...
July 12, 2017: Journal of Theoretical Biology
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