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Uso de técnicas computacionais no estudo da transcrição e regulação gênica em Homo sapiens e Mus musculus; Use of computational methods to study the transcription and gene regulation in Homo sapiens and Mus musculus

Galante, Pedro Alexandre Favoretto
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 18/01/2008 PT
Relevância na Pesquisa
55.95%
O gene, uma seqüência de nucleotídeos necessária para a síntese de moléculas funcionais, é transcrito e regulado por um conjunto de processos e fatores extremamente complexos. Entender o momento e o tecido em que os genes são expressos, as isoformas funcionais, as regiões controladoras e os fatores envolvidos na regulação da expressão de cada gene é um dos grandes desafios da biologia molecular moderna. Hoje, com a enorme quantidade de informações de seqüências genômicas e de transcriptomas, aliado ao desenvolvimento de métodos computacionais para agrupar e analisar estes dados em larga escala, o estudo dos fenômenos relacionados à transcrição e regulação gênica está passando por uma revolução. Por exemplo, é possível medir, concomitantemente, a expressão gênica de milhares de genes em diferentes tecidos, assim como identificar diversos fenômenos que atuam nestes genes. Neste trabalho nós desenvolvemos e aplicamos métodos computacionais no estudo de quatro temas envolvendo aspectos chave da transcrição e regulação gênica. No primeiro trabalho, nós abordamos a expressão gênica tecido-específica através do estudo dos genes expressos no cérebro e em dez regiões cerebrais de camundongo. No segundo trabalho...

Simetrias de Lie e modelagem estocástica da regulação da expressão gênica; Lie symmetries and stochastic modeling of gene expression regulation

Ramos, Alexandre Ferreira
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 16/09/2008 PT
Relevância na Pesquisa
55.94%
Nesta tese, mostramos que o modelo estocástico binário para expressão gênica, por um gene auto-regulado, possui solução completa. A solução dependente do tempo é escrita via expansão em termos das funções de Heun confluentes. Apresentamos um exemplo de dinâmica estocástica desse gene. Para tal, desenvolvemos uma relação de recorrência entre derivadas arbitrárias das funções de Heun confluentes. Mostramos também que o regime estacionário deste modelo possui simetria de Lie SO(2, 1) tipo Lorentz. Esta simetria é análoga à simetria do momento angular, porém com um sinal errado. O invariante desta álgebra define a meia-vida relativa do regime dinâmico do gene. O equivalente do momento angular azimutal é uma medida indireta do nível de atividade do gene. Os operadores levantamento e abaixamento conectam diferentes processos estocásticos de expressão proteínica. As flutuações destes processos estocásticos são classificadas em termos das relações entre os etiquetadores de um elemento da representação da álgebra. No arcabouço da teoria dos grupos, o modelo estocástico para um gene externamente regulado aparece como um caso particular do modelo para um gene auto-regulado. Mostramos, por fim, uma comparação entre estas duas estratégias de regulação. Demonstramos que um gene auto-regulado pode expressar proteínas em regimes sub Poisson...

Environmental exposures and gene regulation in disease etiology

Edwards,Thea M.; Myers,John Peterson
Fonte: ABRASCO - Associação Brasileira de Saúde Coletiva Publicador: ABRASCO - Associação Brasileira de Saúde Coletiva
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/02/2008 EN
Relevância na Pesquisa
65.85%
Health or disease is shaped for all individuals by interactions between their genes and environment. Exactly how the environment changes gene expression and how this can lead to disease are being explored in a fruitful new approach to environmental health research, representative studies of which are reviewed here. We searched Web of Science and references of relevant publications to understand the diversity of gene regulatory mechanisms affected by environmental exposures with disease implications. Pharmaceuticals, pesticides, air pollutants, industrial chemicals, heavy metals, hormones, nutrition, and behavior can change gene expression through a broad array of gene regulatory mechanisms. Furthermore, chemically induced changes in gene regulation are associated with serious and complex human diseases, including cancer, diabetes and obesity, infertility, respiratory diseases, allergies, and neurodegenerative disorders such as Parkinson and Alzheimer diseases. The reviewed studies indicate that genetic predisposition for disease is best predicted in the context of environmental exposures. And the genetic mechanisms investigated in these studies offer new avenues for risk assessment research. Finally, we are likely to witness dramatic improvements in human health...

Characterization of Transcriptional Regulation of Shewanella frigidimarina Fe(III)-Induced Flavocytochrome c Reveals a Novel Iron-Responsive Gene Regulation System

Reyes-Ramirez, Francisca; Dobbin, Paul; Sawers, Gary; Richardson, David J.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /08/2003 EN
Relevância na Pesquisa
65.89%
The bacterium Shewanella frigidimarina can grow anaerobically by utilizing Fe(III) as a respiratory electron acceptor. This results in the synthesis of a number of periplasmic c-type cytochromes, which are absent when the organism is grown in the absence of added Fe(III). One cytochrome, IfcA, is synthesized when Fe(III) is present as the sole respiratory electron acceptor or when it is present in combination with oxygen, fumarate, or nitrate. The ifcA gene was thus selected for a study of iron-responsive gene regulation of respiratory proteins in S. frigidimarina. The monocistronic ifcA gene clusters with two other monocistronic genes, ifcO, encoding a putative outer membrane porin, and ifcR, encoding a putative transcriptional regulator of the LysR superfamily. Analysis of transcription of all three genes under a range of growth conditions in the wild type and an ifcR insertion mutant and analysis of a strain that constitutively expresses ifcR revealed that iron regulation is exerted at the level of ifcR transcription. In the presence of Fe(III) IfcR is synthesized and acts positively to regulate expression of ifcO and ifcA. Control of Fe(III) respiration by this novel regulatory system differs markedly from Fur-mediated regulation of iron assimilation...

Arginine-Dependent Gene Regulation via the ArgR Repressor Is Species Specific in Chlamydia

Schaumburg, Chris S.; Tan, Ming
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /02/2006 EN
Relevância na Pesquisa
65.81%
Some, but not all, Chlamydia spp. are predicted to encode a homolog of ArgR, a master regulatory molecule that modulates arginine biosynthesis and catabolism in bacteria in response to intracellular arginine levels. While genes for arginine biosynthesis are apparently missing in Chlamydia, a putative arginine transport system encoded by glnP, glnQ, and artJ is present. We found that recombinant Chlamydia pneumoniae ArgR functions as an arginine-dependent aporepressor that bound specifically to operator sequences upstream of the glnPQ operon. ArgR was able to repress transcription in a promoter-specific manner that was dependent on the concentration of the corepressor l-arginine. We were able to locate ArgR operators upstream of glnPQ in C. pneumoniae and Chlamydophila caviae but not Chlamydia trachomatis, which corresponded to the predicted presence or absence of ArgR in these chlamydial species. Our findings indicate that only some members of the family Chlamydiaceae have an arginine-responsive mechanism of gene regulation that is predicted to control arginine uptake from the host cell. This is the first study to directly demonstrate a species-specific mechanism of transcriptional regulation in Chlamydia.

Specific Interactions between Four Molybdenum-Binding Proteins Contribute to Mo-Dependent Gene Regulation in Rhodobacter capsulatus▿

Wiethaus, Jessica; Müller, Alexandra; Neumann, Meina; Neumann, Sandra; Leimkühler, Silke; Narberhaus, Franz; Masepohl, Bernd
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
65.82%
The phototrophic purple bacterium Rhodobacter capsulatus encodes two transcriptional regulators, MopA and MopB, with partially overlapping and specific functions in molybdate-dependent gene regulation. Both MopA and MopB consist of an N-terminal DNA-binding helix-turn-helix domain and a C-terminal molybdate-binding di-MOP domain. They formed homodimers as apo-proteins and in the molybdate-bound state as shown by yeast two-hybrid (Y2H) studies, glutaraldehyde cross-linking, gel filtration chromatography, and copurification experiments. Y2H studies suggested that both the DNA-binding and the molybdate-binding domains contribute to dimer formation. Analysis of molybdate binding to MopA and MopB revealed a binding stoichiometry of four molybdate oxyanions per homodimer. Specific interaction partners of MopA and MopB were the molybdate transporter ATPase ModC and the molbindin-like Mop protein, respectively. Like other molbindins, the R. capsulatus Mop protein formed hexamers, which were stabilized by binding of six molybdate oxyanions per hexamer. Heteromer formation of MopA and MopB was shown by Y2H studies and copurification experiments. Reporter gene activity of a strictly MopA-dependent mop-lacZ fusion in mutant strains defective for either mopA...

Regulatory consequences of gene translocation in bacteria

Block, Dena H. S.; Hussein, Razika; Liang, Lusha W.; Lim, Han N.
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
55.91%
Gene translocations play an important role in the plasticity and evolution of bacterial genomes. In this study, we investigated the impact on gene regulation of three genome organizational features that can be altered by translocations: (i) chromosome position; (ii) gene orientation; and (iii) the distance between a target gene and its transcription factor gene (‘target-TF distance’). Specifically, we quantified the effect of these features on constitutive expression, transcription factor binding and/or gene expression noise using a synthetic network in Escherichia coli composed of a transcription factor (LacI repressor) and its target gene (yfp). Here we show that gene regulation is generally robust to changes in chromosome position, gene orientation and target-TF distance. The only demonstrable effect was that chromosome position alters constitutive expression, due to changes in gene copy number and local sequence effects, and that this determines maximum and minimum expression levels. The results were incorporated into a mathematical model which was used to quantitatively predict the responses of a simple gene network to gene translocations; the predictions were confirmed experimentally. In summary, gene translocation can modulate constitutive gene expression levels due to changes in chromosome position but it has minimal impact on other facets of gene regulation.

The mechanisms of genome-wide target gene regulation by TCF7L2 in liver cells

Norton, Luke; Chen, Xi; Fourcaudot, Marcel; Acharya, Nikhil K.; DeFronzo, Ralph A.; Heikkinen, Sami
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
65.92%
In the liver Wnt-signaling contributes to the metabolic fate of hepatocytes, but the precise role of the TCF7L2 in this process is unknown. We employed a temporal RNA-Seq approach to examine gene expression 3–96 h following Tcf7l2 silencing in rat hepatoma cells, and combined this with ChIP-Seq to investigate mechanisms of target gene regulation by TCF7L2. Silencing Tcf7l2 led to a time-dependent appearance of 406 differentially expressed genes (DEGs), including key regulators of cellular growth and differentiation, and amino acid, lipid and glucose metabolism. Direct regulation of 149 DEGs was suggested by strong proximal TCF7L2 binding (peak proximity score > 10) and early mRNA expression changes (≤18 h). Indirect gene regulation by TCF7L2 likely occurred via alternate transcription factors, including Hnf4a, Foxo1, Cited2, Myc and Lef1, which were differentially expressed following Tcf7l2 knock-down. Tcf7l2-silencing enhanced the expression and chromatin occupancy of HNF4α, and co-siRNA experiments revealed that HNF4α was required for the regulation of a subset of metabolic genes by TCF7L2, particularly those involved in lipid and amino-acid metabolism. Our findings suggest TCF7L2 is an important regulator of the hepatic phenotype...

The Krüppel-associated box repressor domain induces reversible and irreversible regulation of endogenous mouse genes by mediating different chromatin states

Ying, Yue; Yang, Xingyu; Zhao, Kai; Mao, Jifang; Kuang, Ying; Wang, Zhugang; Sun, Ruilin; Fei, Jian
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
55.91%
The Krüppel-associated box (KRAB) domain is a transcription repression module from the largest family of transcriptional regulators encoded by higher vertebrates. We developed a drug-controllable regulation system based on an artificial KRAB-containing repressor (tTS) that targets the endogenous Hprt gene to explore the regulatory mechanism and molecular basis of KRAB-containing regulators within the context of an endogenous gene in vivo. We show that KRAB can mediate irreversible and reversible regulation of endogenous genes in mouse that is dependent on embryonic developmental stage. KRAB-induced stable DNA methylation within the KRAB binding region during the early embryonic stage, resulting in irreversible gene repression. In later stages, KRAB mainly induced de-acetylation and methylation of histone, resulting in reversible gene repression. Thus, we have characterized the KRAB-mediated regulation system within the context of an endogenous gene and multiple spatiotemporal ranges, thereby providing a basis for identifying the function of KRAB-containing regulators and aiding development of novel KRAB-based gene regulation tools in vivo.

The chromatin architectural proteins HMGD1 and H1 bind reciprocally and have opposite effects on chromatin structure and gene regulation

Nalabothula, Narasimharao; McVicker, Graham; Maiorano, John; Martin, Rebecca; Pritchard, Jonathan K; Fondufe-Mittendorf, Yvonne N
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
55.91%
Background: Chromatin architectural proteins interact with nucleosomes to modulate chromatin accessibility and higher-order chromatin structure. While these proteins are almost certainly important for gene regulation they have been studied far less than the core histone proteins. Results: Here we describe the genomic distributions and functional roles of two chromatin architectural proteins: histone H1 and the high mobility group protein HMGD1 in Drosophila S2 cells. Using ChIP-seq, biochemical and gene specific approaches, we find that HMGD1 binds to highly accessible regulatory chromatin and active promoters. In contrast, H1 is primarily associated with heterochromatic regions marked with repressive histone marks. We find that the ratio of HMGD1 to H1 binding is a better predictor of gene activity than either protein by itself, which suggests that reciprocal binding between these proteins is important for gene regulation. Using knockdown experiments, we show that HMGD1 and H1 affect the occupancy of the other protein, change nucleosome repeat length and modulate gene expression. Conclusion: Collectively, our data suggest that dynamic and mutually exclusive binding of H1 and HMGD1 to nucleosomes and their linker sequences may control the fluid chromatin structure that is required for transcriptional regulation. This study provides a framework to further study the interplay between chromatin architectural proteins and epigenetics in gene regulation.

A framework for modelling gene regulation which accommodates non-equilibrium mechanisms

Ahsendorf, Tobias; Wong, Felix; Eils, Roland; Gunawardena, Jeremy
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
65.9%
Background: Gene regulation has, for the most part, been quantitatively analysed by assuming that regulatory mechanisms operate at thermodynamic equilibrium. This formalism was originally developed to analyse the binding and unbinding of transcription factors from naked DNA in eubacteria. Although widely used, it has made it difficult to understand the role of energy-dissipating, epigenetic mechanisms, such as DNA methylation, nucleosome remodelling and post-translational modification of histones and co-regulators, which act together with transcription factors to regulate gene expression in eukaryotes. Results: Here, we introduce a graph-based framework that can accommodate non-equilibrium mechanisms. A gene-regulatory system is described as a graph, which specifies the DNA microstates (vertices), the transitions between microstates (edges) and the transition rates (edge labels). The graph yields a stochastic master equation for how microstate probabilities change over time. We show that this framework has broad scope by providing new insights into three very different ad hoc models, of steroid-hormone responsive genes, of inherently bounded chromatin domains and of the yeast PHO5 gene. We find, moreover, surprising complexity in the regulation of PHO5...

Computational Approaches for Analyzing the Role of Protein-DNA Interactions in Gene Regulation; Theoretische Ansätze zur Analyse der Rolle von Protein-DNA-Wechselwirkungen in der Genregulation

Höglund, Annette
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
EN
Relevância na Pesquisa
66.03%
Gene regulation plays a pivotal role at all stages of organism development, in cell differentiation, and for maintaining homeostasis. Controlled spatial and temporal gene expression is achieved by means of complex and robust regulatory networks. A key event in maintaining such networks is the sequence specific protein-DNA recognition, which enables transcription factors to identify their respective binding sites. Computational and structural biologists face intriguing challenges at three different levels when investigating gene regulation. First, the involvement of gene regulation in disease can be addressed by studying global effects of gene regulatory networks, which are visible at the level of systems. Furthermore, detecting the often short and variable transcription factor binding sites (TFBSs) in genomic DNA is not a trivial task, since the prediction of TFBSs and delineation of functional regulatory modules are conducted at the level of sequences. Finally, there is a challenge in understanding the factors governing transcription factor-DNA recognition, as the information needs to be collected at the molecular level. Structure-based methods provide detailed information about protein-DNA interactions at atomic resolution. In this work...

EVOLUTION OF DEVELOPMENTAL GENE REGULATION IN THE MYXOBACTERIA

Chen, I-Chen
Fonte: [Bloomington, Ind.] : Indiana University Publicador: [Bloomington, Ind.] : Indiana University
Tipo: Doctoral Dissertation
Relevância na Pesquisa
65.77%
A rapidly growing body of evidence has shown that non-coding small RNAs (sRNAs) regulate a variety of important biological processes across all domains of life, including bacteria. The sRNA Pxr in the model myxobacterial species Myxococcus xanthus functions as a developmental gatekeeper that prevents the initiation of fruiting body development until nutrients have been depleted. My dissertation research has focused on the origin and evolution of Pxr and its associated regulatory network in the myxobacteria. Using a combination of phylogenetic and molecular-genetic approaches, I tracked the origin of Pxr and examined its evolution at both sequence and functional levels in the myxobacteria. I showed that Pxr appears to have a single origin at the base of the suborder Cystobacterineae within the Myxococcocales (myxobacteria) order. Homologs of pxr are highly conserved and may play a common fundamental role in regulating fruiting body formation across diverse species of myxobacteria. Nevertheless, pxr duplications occurred in the genus Cystobacter and the specificity of its function may be evolving in these lineages. Further, following from a previous mutagenesis screen to identify genes involved in the Pxr regulatory pathway, I identified four genes that appeared to have important roles in the Pxr pathway. I characterized the evolutionary divergence of these genes across species and functional roles of some of these genes in Pxr synthesis...

DNA compaction induced by a cationic polymer or surfactant impact gene expression and DNA degradation

Ainalem, Marie-Louise; Bartles, Andrew; Muck, Joscha; Dias, Rita S.; Carnerup, Anna M.; Zink, Daniele; Nylander, Tommy
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica Formato: 12 pages
Relevância na Pesquisa
55.92%
There is an increasing interest in achieving gene regulation in biotechnological and biomedical applications by using synthetic DNA-binding agents. Most studies have so far focused on synthetic sequence-specific DNA-binding agents. Such approaches are relatively complicated and cost intensive and their level of sophistication is not always required, in particular for biotechnological application. Our study is inspired by in vivo data that suggest that DNA compaction might contribute to gene regulation. This study exploits the potential of using synthetic DNA compacting agents that are not sequence-specific to achieve gene regulation for in vitro systems. The semi-synthetic in vitro system we use include common cationic DNA-compacting agents, poly(amido amine) (PAMAM) dendrimers and the surfactant hexadecyltrimethylammonium bromide (CTAB), which we apply to linearized plasmid DNA encoding for the luciferase reporter gene. We show that complexing the DNA with either of the cationic agents leads to gene expression inhibition in a manner that depends on the extent of compaction. This is demonstrated by using a coupled in vitro transcription-translation system. We show that compaction can also protect DNA against degradation in a dose-dependent manner. Furthermore...

Flexibility and Disorder in Gene Regulation: LacI/GalR and Hox Proteins

Bondos, Sarah E.; Swint-Kruse, Liskin; Matthews, Kathleen S.
Fonte: Universidade Rice Publicador: Universidade Rice
Tipo: Journal article; Text; post-print
ENG
Relevância na Pesquisa
65.8%
To modulate transcription, a variety of input signals must be sensed by genetic regulatory proteins. In these proteins, flexibility and disorder are emerging as common themes. Prokaryotic regulators generally have short, flexible segments, whereas eukaryotic regulators have extended regions that lack predicted secondary structure (intrinsic disorder). Two examples illustrate the impact of flexibility and disorder on gene regulation: the prokaryotic LacI/GalR family, with detailed information from studies on LacI, and the eukaryotic family of Hox proteins, with specific insights from investigations of Ultrabithorax (Ubx). The widespread importance of structural disorder in gene regulatory proteins may derive from the need for flexibility in signal response and, particularly in eukaryotes, in protein partner selection.

Studies on Transcriptional Regulation in the Human Retina: Mapping of Transcriptional Start Sites of Retinal Expressed Genes and Functional Characterization of the CNGA3 promoter; Untersuchungen zur Regulierung der Transkription in der humanen Retina: Kartierung von Transkriptionsstartpunkten retinal exprimierter Gene und funktionale Charakterisierung des CNGA3-Promotors

Carpio Farro, Ronald Erick
Fonte: Universität Tübingen Publicador: Universität Tübingen
Tipo: Dissertation; info:eu-repo/semantics/doctoralThesis
EN
Relevância na Pesquisa
55.94%
Background The proper assembly of the transcriptional initiation machinery is a key regulatory step in the execution of the correct program of mRNA synthesis. The use of alternative transcription start sites (TSSs) provides a mechanism for cell and tissue specific gene regulation. Our knowledge of transcriptional initiation sequences in the human genome is limited despite the availability of the complete genome sequence. While genome wide experimental and bioinformatic approaches are improving our knowledge of TSSs, they lack information concerning genes expressed in a restricted manner or at very low levels, such as tissue specific genes, such as retinal genes. The importance of this work is that new TSSs and transcribed sequences are essential for further exploration of the promoter and other cis-regulatory sequences at the 5´end of genes. In this study we further characterize the promoter of the CNGA3 gene. Chapter I: Identification of the Transcription Start Sites (TSSs) in human retinal expressed genes The first part of this work was dedicated to the identification of TSSs of human retinal expressed genes and to improve and complete gene annotation concerning the 5’-UTR. This work was based on the following goals: - In silico analysis of ESTs and known algorithm predictions of genes expressed in human retina to select the best candidate genes for TSS experimental study. - Comparison of whole available pull of mRNA transcripts in order to understand and predict potential alternative TSSs for human retinal expressed genes. - Experimental validation via Cap-finder RACE mapping of the TSSs of selected human retinal expressed genes. - Analysis of the selectivity of genes for TSSs on human retinal tissue. This work reports the mapping of TSSs of 54 retina expressed genes: This means new sequences for 41 genes of them. Results analysis and classification put those 41 genes into five categories (i) TSS located in new first exons...

Modeling cooperative gene regulation using Fast Orthogonal Search

Minz, Ian
Fonte: Quens University Publicador: Quens University
Tipo: Tese de Doutorado Formato: 1393554 bytes; application/pdf
EN; EN
Relevância na Pesquisa
65.82%
A number of computational methods have suggested means by which gene transcription – the process through which RNA is created from DNA – is activated, but there are factors at work that no model has been able to fully explain. In eukaryotes, gene regulation is quite complex, so models have primarily focused on a relatively simple species, Saccharomyces cerevisiae (budding yeast). Because of the inherent complexity in higher species, and even in yeast, a method of identifying transcription factor (TF) binding motifs (specific, short DNA sequences) must be efficient and thorough in its analysis. This thesis shows that a method using the Fast Orthogonal Search (FOS) algorithm to uncover binding motifs as well as cooperatively binding groups of motifs can explain variations in gene expression profiles, which reflect the level at which DNA is transcribed into RNA for a number of genes. The algorithm is very fast, exploring a motif list and constructing a final model within seconds to a few minutes. It produces model terms that are consistent with known motifs, while also revealing new motifs and interactions, and it causes impressive reductions in variance with relatively few model terms over the cell-cycle.; Thesis (Master, Electrical & Computer Engineering) -- Queen's University...

Morphological innovation through gene regulation: an example from Devonian Onychodontiform fish

Campbell, Kenton; Barwick, Richard
Fonte: UBC Press Publicador: UBC Press
Tipo: Artigo de Revista Científica
Relevância na Pesquisa
65.85%
The recent development of novel phenotypic designs by changes in gene regulation has been extensively discussed within the context of evolution and development. The fossil record shows many new designs (or body plans) which appear rapidly at various strat

Light-Inducible Gene Regulation in Mammalian Cells

Toth, Lauren Polstein
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação
Publicado em //2015
Relevância na Pesquisa
66%

The growing complexity of scientific research demands further development of advanced gene regulation systems. For instance, the ultimate goal of tissue engineering is to develop constructs that functionally and morphologically resemble the native tissue they are expected to replace. This requires patterning of gene expression and control of cellular phenotype within the tissue engineered construct. In the field of synthetic biology, gene circuits are engineered to elucidate mechanisms of gene regulation and predict the behavior of more complex systems. Such systems require robust gene switches that can quickly turn gene expression on or off. Similarly, basic science requires precise genetic control to perturb genetic pathways or understand gene function. Additionally, gene therapy strives to replace or repair genes that are responsible for disease. The safety and efficacy of such therapies require control of when and where the delivered gene is expressed in vivo.

Unfortunately, these fields are limited by the lack of gene regulation systems that enable both robust and flexible cellular control. Most current gene regulation systems do not allow for the manipulation of gene expression that is spatially defined, temporally controlled...

Environmental exposures and gene regulation in disease etiology

Edwards,Thea M.; Myers,John Peterson
Fonte: ABRASCO - Associação Brasileira de Saúde Coletiva Publicador: ABRASCO - Associação Brasileira de Saúde Coletiva
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/02/2008 EN
Relevância na Pesquisa
65.85%
Health or disease is shaped for all individuals by interactions between their genes and environment. Exactly how the environment changes gene expression and how this can lead to disease are being explored in a fruitful new approach to environmental health research, representative studies of which are reviewed here. We searched Web of Science and references of relevant publications to understand the diversity of gene regulatory mechanisms affected by environmental exposures with disease implications. Pharmaceuticals, pesticides, air pollutants, industrial chemicals, heavy metals, hormones, nutrition, and behavior can change gene expression through a broad array of gene regulatory mechanisms. Furthermore, chemically induced changes in gene regulation are associated with serious and complex human diseases, including cancer, diabetes and obesity, infertility, respiratory diseases, allergies, and neurodegenerative disorders such as Parkinson and Alzheimer diseases. The reviewed studies indicate that genetic predisposition for disease is best predicted in the context of environmental exposures. And the genetic mechanisms investigated in these studies offer new avenues for risk assessment research. Finally, we are likely to witness dramatic improvements in human health...