Dissertations / Theses on the topic 'Réseau transcriptionnel'
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Carat, Solenne. "Génomique intégrative du coactivateur transcriptionnel PRC." Nantes, 2010. https://archive.bu.univ-nantes.fr/pollux/show/show?id=e47e15ea-a685-4ec3-9239-0a8bf6758367.
Full textEmergence over the last few years of high throughput technologies like DNA microarray and more recently next generation sequencing now allows an exhaustive analysis of genome with several regulation levels including expression measure of all cell genes, DNA – transcription factors interactions, and also DNA methylation. It thus becomes indispensable to integrate these different data to be able to understand and then to model all these mechanisms involved in global cell function. This understanding will then enable to apprehend the sources of deregulation involved in many pathologies. The goal of my PhD is to understand the impact of PRC (PGC-1 Related Coactivator) transcriptional coactivator on the coordination of mitochondrial and cellular proliferation, from human tumor cell line XTC. UC1, rich in mitochondria. To do so, PRC and transcription factors ERRa, NRF1, GABP, CREB and YY1 involved in these two processes have been studied with ChIP-chip. Positive genes for these transcription factors are then compared with transcriptome of the same cells under siRNA PRC effects. Integration of these different data of transcriptome and ChIP-chip, coupled with study of motifs discovery, will allow to construct the transcriptional regulatory networks necessary to the understanding of PRC pathways. These networks will make possible the detection of therapeutic targets allowing to correct pathological condition
Oldfield, Andrew. "Etude du réseau transcriptionnel du gène Xist, acteur principal de l'inactivation du chromosome X." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2010. http://tel.archives-ouvertes.fr/tel-00815096.
Full textDeyell, Matthew. "Multiplexed Genetic Perturbations of the Regulatory Network of E. coli." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCC175/document.
Full textDespite advances in DNA sequencing, we have yet to understand how an organism’s phenotype relates to the contents of their genome. However it has become clear that the impact of genes are context dependant. The mere presence of a gene within a genome does not inform us of when it is expressed, and which other genes are expressed along with it. Understanding how gene expression is regulated is a necessary piece of understanding how phenotypes emerge from a given genotype. Transcription factors, which can activate or repress the expression of a gene, form a complex network of interactions between themselves and their targeted genes. This network consists of a hierarchy of groups of strongly connected transcription factors, each relating to distinct cellular processes. Is the structure of this transcriptional regulatory network significant to the transcriptional response of a cell? Here we use a programmable DNA binding protein called CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) to perturb gene expression of global regulators within the transcriptional regulatory network. These global regulators are regulating many distinct cellular processes and have many genetic targets. The CRISPR system allows us to perturb these regulators in all possible combinations, including higher order perturbations with potentially all targeted global regulators perturbed at the same time. We then record both the expression pattern of the transciptome using RNA sequencing, and the fitness of each strain. We find that the structure of the regulatory network increases the dimensionality of the transcriptional response rather than reducing it. This results in significant high order epistasis beyond pair-wise interactions. This has implications for how these networks evolve. The pair-wise epistasis we find between global transcription factors rely on the presence or absence of other perturbations. This implies that other perturbations could act as potentiating mutations. The number of potential evolutionary paths increases with high order epistasis, although this alone tells us nothing about the quality of those paths. Importantly, the replicates for this thesis are still on-going and the data presented here has not yet excluded experimental artefacts
Sultan, Islam. "La construction du réseau de régulation transcriptionnelle." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS184/document.
Full textThis PhD project takes place in List MAPS, a Horizon 2020-funded Marie Curie Actions InnovativeTraining Network (ITN) with the goal of understandingof the ecology of Listeria monocytogenesthrough the combination of high throughput Epigenetics, Deep sequencing of transcripts, Proteomics, Bioinformatics, Mathematics and Microbiology. Acentralobjective of the ITN is to decipher the mechanismsunderlying adaptation and virulence of L. monocytogenes“from farm to fork”.This PhD project (subproject9) aims to tackle the task of transcription regulatorynetwork construction. A significant part of regulationat the transcriptional level is achieved by modulationof transcription initiation rate. In bacteria, transcriptioninitiation relies on recognition of particular sequencemotif by a Sigma-factor approximately 10 bpupstream of the transcription start site (TSS) and ismodulated by the binding of transcription factors recognizingother sequence motifs located nearby. RNASeqtranscriptomics provides direct information on therepertoire of TSSs and transcription units and therebyoffers renewed perspectives to address the problemof transcription factor binding sites identification. Thegoal of this PhD project is to assess existing toolsand to develop new methods for prediction of TF bindingsites by combining expression profiles and preciseinformation on the location of the TSSs. Severalapproaches based on position weight matrix (PWM)models will be investigated to extend the classicalmixture model by relaxing the hypothesis that motifscorresponding to different TF binding sites occur independentlybetween TSS regions.In the new model,we will explicitly account for the increased probabilityof occurrence of a same motif in two promoters whentheir profiles of activity across conditions are similar. A particular attention will also be paid to the positionof the motif with respect to the TSS and the sigmafactor binding site. In parallel to the methodologicaldevelopments we will also work on the use of theseapproaches to build the transcription regulatory networkof L. monocytogenes based on data form theliterature and from the List MAPS project. Finally, wewish to use the information on the regulatory networkto tackle a particular point relevant for the List MAPSproject using a dedicated model
Vallat, Laurent. "Réseaux de régulation transcriptionnelle de la leucémie lymphode chronique." Paris 7, 2006. http://www.theses.fr/2006PA077174.
Full textChronic lymphocytic leukemia (CLL) is a B lymphoproliferative disorder of unknown mechanism, characterized by a heterogeneous clinical outcome. Cells from the more aggressive CLL subtype show a specific B cell receptor (BCR). The resulting integrated signal from several pathways, such as BC stimulation and DNA damage response, is also impaired contributing to frequent genetic aberrations. CLL cells reveal a specific transcriptional profile compared to other hematopoietic neoplasms. Several transcriptional programs were then studied within different CLL cells subtypes, at the basal level or after cell stimulation. Gene expression comparison before and after DNA damage by ionizing irradiation showed a specific transcriptional response for the apoptosis resistant cells Functional gene product analysis of the more aggressive cells at the basal level or after cell stimulation showed complex disorder of multiple gene expression. Unsupervised gene expression analysis over 6hrs after BCR cross-linking revealed a transcriptional program specific for the more aggressive CLL cells. In order to understand the concerted action of these thousand of genes over time, temporal gene interaction models were inferred. The scale free architecture of these models revealed transcriptional nodes, suggesting rational targets to perturb these pathways in the more aggressive cells
Marois-Blanchet, François-Christophe. "Le rôle de la régulation transcriptionnelle dans l'évolution des réseaux d'interaction protéine-protéine." Thesis, Université Laval, 2011. http://www.theses.ulaval.ca/2011/28445/28445.pdf.
Full textEvolution by gene duplication is considered one of the most important mechanisms of evolutionary innovation. What is less known and highly debated is the relative role of the divergence of transcriptional regulation and the divergence of protein coding sequence in the evolution of molecular networks. We developed a method aimed at evaluating the role of transcriptional regulation in the divergence of protein-protein interactions among duplicated genes in the budding yeast Saccharomyces cerevisiae. Our results demonstrate that our approach can be used effectively to test if divergence of protein-protein interaction profiles can be explained by the divergence of transcriptional regulation or the divergence of coding sequences. We found evidence supporting different scenarios, whereby expression regulation has a large effect, no effect or little effect on protein-protein interaction profiles of paralogous proteins. Our method can be brought to large scale and help elucidate the importance of gene transcriptional regulation in evolution of complex cellular networks.
Lopez, Pierre fabrice. "De l'analyse de la régulation transcriptionnelle à la modélisation logique des réseaux géniques." Aix-Marseille 2, 2009. http://www.theses.fr/2009AIX22064.
Full textThis thesis report is about bioinformatic analysis of mechanisms involved in regulation of gene expression, an ubiquitous phenomenon in all life froms, notably at the root of cellular differenciation. The use of genomic large scale datasets motivated the creation of specific algorithms and methods. These approaches led to the development of tools and databases, namely the software BZScan for the quantification of DNA microarray images, the ATD database listing polyadenylation sites in human and mouse genomes, the sofware package TranscriptomeBrowser containing a transcriptional signatures database, and the logical simultaion and modellind software signatures database, and the logical simulation and modelling software GINsim. A modular programming approach allowed us to develop efficient communication between these different tools
Abou-Jaoude, Wassim. "Oscillations et bistabilité dans des réseaux de régulation transcriptionnelle: étude théorique et expérimentale." Doctoral thesis, Universite Libre de Bruxelles, 2009. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210295.
Full textLa première partie de cette thèse a été consacrée à l’étude du réseau p53-Mdm2 pour lequel nous avons développé un modèle simple composé d’un circuit de rétroaction positif imbriqué dans un circuit de rétroaction négatif. Les résultats de notre analyse logique montrent que les principales propriétés dynamiques du réseau peuvent être résumées par un petit nombre de diagrammes de bifurcation logique. Ces scénarios de bifurcations diffèrent par la séquence d’activation du circuit positif et négatif composant le réseau et dépendent d’une part de l’affinité de la p53 pour ses gènes cibles et d’autre part de son activité transcriptionnelle. Nous proposons que différents stress et types cellulaires pourraient correspondre à différents scénarios de bifurcation et donc conduire à des réponses différentes après irradiation. Cette première analyse qualitative nous a permis de rendre compte de différents aspects de la dynamique du réseau observés expérimentalement, tels que le changement de fréquence des oscillations en cours de réponse, les oscillations de longue durée de la p53 ou l’amortissement rapide des oscillations à l’échelle d’une population de cellules. Pour nous affranchir des fortes non-linéarités inhérentes au traitement logique, nous avons ensuite traduit le modèle logique en un modèle différentiel et montré que les principaux comportements présentés par le modèle logique sont conservés, suggérant que la structure du réseau détermine dans une large mesure les principales potentialités dynamiques du système. L’analyse des propriétés de bifurcation du modèle différentiel en fonction du niveau de dommage à l’ADN nous a également permis de mettre en évidence la présence de deux régimes oscillants d’amplitude, de valeur moyenne et de fréquence nettement différentes, séparés par une zone de bicyclicité où ces deux régimes coexistent. Cette propriété permet d’expliquer l’existence des deux fréquences d’oscillation différentes qui ont été observées expérimentalement en fonction de la dose d’irradiation. Enfin l’analyse stochastique de notre modèle nous a, en particulier, permis de rendre compte de l’augmentation du nombre de cellules oscillant à des fréquences élevées lorsque la dose d’irradiation augmente, observée expérimentalement.
La deuxième partie de notre thèse a été consacrée à l’étude du réseau de facteurs GATA chez la levure S.cerevisiae. Ce réseau, constitué des activateurs Gln3 et Nil1 et des répresseurs Dal80 et Gzf3, comporte plusieurs circuits de rétroaction positifs et négatifs interconnectés. Dans le but d’aider à comprendre le rôle et le fonctionnement du réseau GATA, nous avons effectué une analyse théorique et expérimentale de son comportement dynamique en fonction de la qualité de la source azotée. L’analyse différentielle montre la possibilité d’un comportement bistable dans les milieux de qualité intermédiaire en azote et d’oscillations amorties suite à un transfert nutritionnel d’une condition azotée à une autre, lorsque l’activation des gènes du réseau par Gln3 et Nil1 est synergique ou lorsque le gène Gln3 est supprimé. Gzf3 serait le répresseur clef impliqué dans la bistabilité tandis que Dal80 serait le répresseur clef impliqué dans les comportements oscillants. L’analyse stochastique nous a permis d’étudier l’effet des fluctuations moléculaires sur ces comportements et les distributions de variables importantes du système dans une population de cellules. Pour le modèle synergique de la souche sauvage et celui du mutant gln3°, elle a montré l’existence, dans des milieux de qualité intermédiaire en azote, de deux populations de cellules qui coexistent :une population où l’expression de Dal80 est réprimée, une autre où son expression est activée. Enfin, l’étude de la dynamique du couplage entre la protéine fluorescente Gfp, sous le contrôle du promoteur de DAL80, et le réseau GATA montre que, pour des ordres de grandeur physiologique de la vitesse de disparition de la Gfp, la bimodalité présente au niveau du réseau GATA devrait se refléter au niveau de la Gfp.
Les comportements bistables et oscillants mis en évidence dans notre étude théorique du réseau GATA ont ensuite été testés expérimentalement en suivant la Gfp sous le contrôle du promoteur de DAL80 en fonction de la concentration de la source azotée glutamine. Cette étude expérimentale nous a permis de mettre en évidence l’existence d’oscillations amorties de la fluorescence de la protéine de fusion Dal80-Gfp. De telles oscillations cependant n’ont pas été observées dans les expériences réalisées sur les autres souches testées pour lesquelles le gène de la Gfp est fusionné au promoteur de DAL80. Notre étude expérimentale montre également l’existence, chez la souche sauvage, d’une population unique de cellules fluorescentes quelle que soit la concentration du milieu extérieur en glutamine testé (0.2mM à 10mM). Un modèle additif où l’activation des gènes du réseau par Gln3 et Nil1 n’est pas synergique serait donc en meilleur accord avec nos observations. Chez les souches où le facteur Gln3 est inactivé, par contre, deux populations cellulaires, l’une de forte fluorescence et constituée de cellules de grande taille, l’autre de plus faible fluorescence et constituée de cellules de taille plus petite, coexistent pour des concentrations intermédiaires du milieu extérieur en glutamine. La forte corrélation observée entre la taille et la fluorescence des cellules suggère que le comportement bimodal observé au niveau de la fluorescence est lié au comportement bimodal observé au niveau de la taille. Enfin, un modèle phénoménologique de la croissance cellulaire nous a permis de reproduire l’existence de deux populations cellulaires de taille distincte.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished
Enriquez, Jonathan. "Contrôle transcriptionnel de l'identité musculaire chez la Drosophile." Toulouse 3, 2009. http://thesesups.ups-tlse.fr/734/.
Full textThe complex muscle patterns laid during development of complex animals allow coordinated, stereotyped movements such as those we all make during our daily life. Each muscle develops through the fusion and differentiation of myoblasts to form syncitial myofibres. Myofibres then connect to the skeleton via specific tendon cells. Once formed, each muscle of the body can be uniquely identified by its position, shape, size and skeletal attachments, properties grouped under the term "identity". While the transcriptional control of myogenesis has been extensively studied, the control of muscle identity remains largely unknown. Most of our present knowledge comes from studies on the Drosophila embryonic musculature, where it has been proposed that muscle identity was reflecting the expression of specific combinations of Transcription Factors (TF) in muscle founder myoblasts. Several years ago, our laboratory showed that the TF Collier (Col), the Drosophila ortholog of mammalian Early-B Cell Factor (EBF), was expressed and required in a single somatic muscle, the DA3 (Dorsal Acute 3) muscle, making this muscle a paradigm for investigating the genetic and cellular bases of muscle identity. During the first part of my thesis work, I contributed to show that formation of the DA3 muscle was dependent upon the combinatorial activity of Col and another muscle identity TF, Nautilus/D-MyoD. D-MyoD is the single Drosophila ortholog of the MyoD family of vertebrate b-HLH muscle regulatory factors (MRFs), Myo-D, Myf-5, Myogenin and MRF4. My results showing that D-MyoD and Col each control specific properties of the DA3 muscle represent a first experimental confirmation of the combinatorial control of muscle identity by TFs expressed in founder myoblasts, an hypothesis formulated almost 20 years ago. .
Thiébaut, Antonin. "Transcriptional networks of the stress responses in the human pathogen Candida glabrata." Electronic Thesis or Diss., Sorbonne université, 2018. http://www.theses.fr/2018SORUS485.
Full textCandida glabrata is simultaneously a commensal of human gut and a pathogenic yeast with an increasing prevalence. It is often associated with fatal bloodstream infections, notably because of its ability to resist azole treatments, evade the immune system and easily colonize the human host. Also, it displays incredible abilities to adapt and resist adverse growth conditions. However, little is known about C. glabrata capacities to adapt and the underlying regulations. This assessment led to the implementation of the Candihub project. It aims to describe the mechanisms that allow C. glabrata to survive and thrive as a pathogen and has a focus on the transcriptional regulatory networks promoting the yeast strong resistance to stress. My PhD project was undertaken within the framework of Candihub. I tried to unravel the regulation networks associated to several transcription factors. These factors were chosen because of their key roles in controlling an array of stress responses : iron deprivation, iron excess, oxidative stress, osmotic stress... To achieve that goal, I performed high-throughput transcriptomic (microarrays) and genomic (ChIP -seq) analyses. This led to the construction of a wide network of interactions. Afterwards, I focused on smaller subparts of this network. The first part tackled the role of the CCAAT-Binding Complex in respiration and iron homeostasis. The CBC is very conserved across the fungi. In S. cerevisiae, it controls cellular respiration, while in pathogenic fungi such as C. albicans, it controls the iron homeostasis. We showed that the CBC has a dual role in C. glabrata : it interacts with the regulatory subunit Hap4 to control respiration and it collaborates with Yap5 to act on iron homeostasis. The second part was based on the use of comparative transcriptomics to uncover unknown features of the iron starvation response of C. glabrata. We demonstrated the significance of Aft2 in response to iron starvation and we identified the regulatory network of Aft2. This revealed the involvement of genes responsible for ribosome rescue in the No GO Decay pathway, thus suggesting a link between iron homeostasis and the NGD
Wang, Jingkui. "Dynamical effects of delay, fluctuation and transcriptional pausing on genetic networks." Thesis, Lille 1, 2012. http://www.theses.fr/2012LIL10093/document.
Full textLiving cells can be viewed as dynamical systems and cellular dynamical properties essentially reply on genetic networks. This thesis work is motivated by one striking dynamical behavior of genetic networks, oscillation, and mainly includes three studies. The first study is about the delay that is one of key ingredients of biological oscillation. In mathematical modeling, delay is usually modeled as explicit delay or reaction delay. By studying a minimal genetic network, a self-repressing gene involving various delays, our analytical results reveal the combination principle of various delays and different dynamical influences of explicit and reaction delays on oscillations. The second study is to investigate the dynamical influences of molecular fluctuations on the oscillatory behavior. We develop a cumulant expansion of the master equation and apply it to the self-repressing gene circuit. We find that fluctuations shift significantly the averages of molecular quantities predicted by deterministic models and induce oscillations. In the third study, we investigate the dynamical effects of RNA Polymerase pausing on transcription in using TASEP model. In the limit case where pause duration is short, we can still construct a mean-field model to analyze the transcription rate and site occupation. In the general case where mean-field approach no long applies, we obtain a good understanding of various mechanisms driving the transcription dynamics over the entire range of pause duration, and in particular a theoretical prediction of transcription rate that agrees well with numerical simulations is given
Marc, Philippe. "Analyse bio-informatique des réseaux de régulation transcriptionnels de la levure Saccharomyces cerevisiae grâce aux puces à ADN." Paris 7, 2002. http://www.theses.fr/2002PA077116.
Full textRouault, Hervé. "Réseaux génétiques et dynamique spatio-temporelle d'ensembles cellulaires." Paris 7, 2009. http://www.theses.fr/2009PA077265.
Full textThis thesis presents a series of works dealing with some aspects of development and cellular differentiation. The first part exposes a bioinformatics algorithm, that we have developed, allowing to study the sequences from the genome responsible for the specific expression of genes in the various tissues constituting an organism. It aims at extracting the key components and some syntax of the cis-regulatory sequences. We present its application to the specification of sensory organ precursors in Drosophila melanogaster. A second part consists in the theoretical study of the structure of the networks of interactions between genes and proteins leading to cell fate specification. We have used a method of evolution in silico, to build genetic networks, needing or not cell-cell communication, mimicking cell differentiation. The underlying phenomena are responsible for the settlement and maintenance of the specialized functions of cells. Finally, in a third part, we propose a model of mechanical control of growth, likely to explain several surprising observation in the formation of organs. In particular, we have modeled the proliferation of cells constituting the Drosophila melanogaster wings and propose a mechanism which make the tissue growth rate uniform
Mordelet, Fantine. "Méthodes d'apprentissage statistique à partir d'exemples positifs et indéterminés en biologie." Phd thesis, École Nationale Supérieure des Mines de Paris, 2010. http://pastel.archives-ouvertes.fr/pastel-00566401.
Full textTaffin, de Tilques Mathilde de. "Contrôle transcriptionnel de l'identité musculaire chez la drosophile : modules cis-régulateurs et gènes cibles directs de Collier." Toulouse 3, 2013. http://thesesups.ups-tlse.fr/2232/.
Full textThe COE (Collier/Early B cell Factor) family is a metazoan-specific family of transcription factors (TF) that are involved in the control of numerous biological processes, including hematopoiesis, neurogenesis and muscle identity. Mutant analysis of COE TFs across several organisms showed defects in the specification of different cell types, like neuron subtypes or, in mammalians, B lymphocytes and brown adipocytes. However, the COE target genes are mostly unknown. Drosophila (fruit fly) is an excellent model to study the functional diversity of COE TFs. The core of my PhD work was the identification of Collier direct target genes in the DA3 muscle lineage, and the characterization of the corresponding CRM to better understand how COE proteins activate specific target genes in a tissue-dependent manner. I performed chromatin immuno-precipitation on whole embryos followed by systematic sequencing of the immuno-precipitated fragments (ChIPseq). By bio-informatics, I identified Col in vivo binding motif and showed that Col binding in vivo is context-dependent. Several candidate genes were validated by in situ hybridizations and functional analysis of the Col binding CRM. TF are over-represented among these targets. All together, the results reveal an unexpected complexity of gene regulatory networks that control muscle identity in Drosophila and confirm the critical role for Col in several transcription regulatory networks in the embryo. Considering the evolutionary conservation of COE proteins and their in vivo DNA binding properties, these results bring new insight into the complexity of COE function in other organisms, including mammals
Touleimat, Nizar. "Méthodologie d'extraction et d'analyse de réseaux de régulation de gènes : analyse de la réponse transcriptionnelle à l'irradiation chez S. cerevisiæ." Phd thesis, Université d'Evry-Val d'Essonne, 2008. http://tel.archives-ouvertes.fr/tel-00877095.
Full textTouleimat, Mohamed Nizar. "Méthodologie d'extraction et d'analyse de réseaux de régulation de gènes : analyse de la réponse transcriptionnelle à l'irradiation chez S. cerevisiæ." Thesis, Evry-Val d'Essonne, 2008. http://www.theses.fr/2008EVRY0044/document.
Full textThe cellular response to the DNA damage provoked by irradiation (IR) is relatively well studied, however, many observations show the involvement of the expression of many genes. We propose to identify the different potential patterns of the transcriptional response to IR and to reconstruct a gene regulatory network involved in its control. The first point of this work lies in the exploitation of the gene expression dynamics in conditions of genetic perturbations. The second point lies in the integration of systemic biological informations. We define an approach composed of one step of automated logical deduction of regulations from a strategy of perturbations and two induction steps that allow the analysis of the gene expression dynamics and the extraction of potential regulation from additional data. This approach allowed to identify, for the yeast, a complex response to IR and allowed to propose a regulation model which some relations have been experimentally validated
Vandermoëre, Constant. "Exemples d'oscillateurs génétiques : le gène auto-réprimé à dynamique transcriptionnelle lente et l'oscillateur central de l'horloge circadienne de l'algue Ostreococcus Tauri." Thesis, Lille 1, 2011. http://www.theses.fr/2011LIL10118/document.
Full textGenes located on the DNA macromolecule inside our cells do not onlycarry hereditary information. They also contribute dynamically tobiological functions by synthesizing proteins at a variable rate.Proteins are subject to many nonlinear interactions with other actors,forming vast biochemical networks which may display a number ofcomplex behaviors. In particular, regulation of gene activity (i.e.,of their transcription rate) by specific proteins creates feedbackloops. These loops form genetic networks where a set of genes regulatetheir expressions reciprocally. Recent experimental studies have shown that gene regulation is notalways instantaneous. We have thus studied the influence of anintrinsic transcriptional dynamics in the simple circuit where a geneis repressed by its own protein. We have obtained an analyticalcriterion for the appearance of oscillations, which allows us to showthat oscillations are favored when gene response time is close to acharacteristic value. The time scale thus identified is relevant bothin a deterministic and a stochastic description. Gene regulatory networks are also at work in some biological rhythms,inducing oscillations in the concentrations of some key proteins.These networks then serve as endogeneous clocks, which allow manyliving organisms to anticipate periodic changes in the environment. Inparticular, the circadian clock is used by organisms to adapt to thediurnal cycle by being entrained by the day/night cycle. Using experimental data, we have constructed a mathematical model ofthe circadian clock of the unicellular alga Ostreococcus tauri.This model is based on a transcriptional negative feedback loop, whichinvolves two genes regulating each other. Agreement between numericalsimulations and experimental data is excellent and unveils the factthat there is no signature of coupling in data when the clock is ontime. This reveals a strong robustness to daylight fluctuations
De, Dieuleveult Maud. "Implication des factures de remodelage de chromatine de la famille CHD dans les réseaux de régulation transcriptionnelle des cellules souches embryonnaires." Phd thesis, Université Paris Sud - Paris XI, 2010. http://tel.archives-ouvertes.fr/tel-00555030.
Full textDieuleveult, Maud de. "Implication des facteurs de remodelage de chromatine de la famille CHD dans les réseaux de régulation transcriptionnelle des cellules souches embryonnaires." Paris 11, 2010. https://tel.archives-ouvertes.fr/tel-00555030.
Full textA new peroxidase was purified from garlic bulbs (POX1B) with interesting biochemical properties compared to HRP. In fact, POX1B is highly active at acidic pH and stable vs. Temperature and storage. The optimal pH was around 5 and the optimal temperature was 30°C. Studies of the heat-stability demonstrated that almost 70 % of the initial activity was conserved at 60°C and full activity was retained at 50 and 40°C for 40 min. Then, the structure-function relationship was investigated by analysis of the spectroscopic properties and correlated to the structure determined by a new generation of high performance hybrid mass spectrometer. Studies of the chemical structure showed that the heme group of this protein is pentacoordinated and has a histidine as proximal ligand. Native and reconstituted POX1B exhibited high affinity towards hydrogen peroxide as well as various reducing co-substrates. In addition, high enzyme specificity was demonstrated. The kcat/KM values were 413. 28, 403. 81 mM-1s-1 for TMB and ABTS, respectively. Furthermore, the reduction of nitro compounds in presence of POX1B was demonstrated by iron(II)-nitrosoalkane complexes assay. POX1B showed a great potential to be applied for drug metabolism since its ability to react with 1-nitrohexane in presence of sodium dithionite was demonstrated by the appearance of a characteristic Soret band at 411 nm. Besides, the high catalytic efficiency obtained in the case of the new garlic peroxidase (POX1B) is suitable for different analytes monitoring and biocatalysis. The enzyme has shown a good potential for electrochemical detection of hydrogen peroxide and chlorophenols. The enzyme immobilization was carried out using chitosan as biopolymer. Electrochemical assays showed that the biosensor was able to monitor H2O2 as low as 100 nM in direct detection mode. The measured detection limit was 30 μM in milk samples with a response time less than 1 min. Then, the electrocatalytic activity of a second POX1B-based biosensor towards chlorophenols derivatives in a large range from 10 pM to 10 μM was demonstrated. The mediator free POX1B-based biosensor exhibited high sensitivity towards 2,6-dichlorophenol, 4-chlorophenol and pentachlorophenol. A detection limit of 1 pM in the case of 4-chlorophenol was demonstrated with kinetic constant Km,app of 0. 42 μM and high rapidity of electrochemical response of the biosensor of 1 s
Saison-Ridinger, Maya. "Rôle du facteur de transcription Spi-1/PU. 1 dans la progression leucémique : dérégulation des réseaux transcriptionnnels et inhibition de l'apoptose." Paris 7, 2012. http://www.theses.fr/2012PA077034.
Full textThe erythroleukemia developed by Spi-1/PU. L transgenic mice is a multistage process. This model recapitulates the co-operation of two mutations occurring during human acute myeloid leukemia progression: a mutation interfering with differentiation and a mutation conferring a proliferative advantage to cells. Overexpression of Spi-1 transcription factor induces differentiation blockage, résistance to apoptosis and an increase in the replication fork speed that exacerbates the genetic instability. To define molecular mechanism involved in Spi-1 oncogenic functions, we explored, by high-through methods, the DNA binding specificities of Spi-1 in erythroleukemic cells in relation to its capacity to activate or repress transcription. Our results reveal distinct mechanisms for transcriptional repression and activation by Spi-1. In erythroleukemic cells, Spi-1 favors gene expression through tight multiple bindings in regions proximal to the transcription start site. We show that Spi-1 protects erythroleukemic cells from apoptosis in vitro and in vivo through inhibition of the bim pro-apoptotic gene expression. The bim expression is inhibited by an epigenetic mechanism involving tri-methylation of Histone 3 at lysine 27 (H3K27me3) on its promoter. Our study suggests a new mechanism for gene repression by Spi-1: the recruitment of the protein complex responsible for H3K27 tri-methylation to promoters
Schleiss, Cédric. "Anomalies des programmes de réponse lymphocytaire après stimulation du récepteur à l’antigène dans la leucémie lymphoïde chronique." Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAJ133.
Full textA cell constantly receives signals from its environment. This stimulation induces a signalling cascade activating a dynamic genic and proteomic program, leading to an adapted cellular response. In chronic lymphocytic leukemia (CLL), an antigen receptor stimulation induces a program and an abnormal response behind leukemic proliferation. Our aim was to characterize the pathological cell program. To achieve this, we have implemented a stimulation model to reproduce ex vivo antigen receptor stimulation of primary cells from CLL patients and activate this cellular program. We then analyzed the transcriptional and proteomic dynamics activated in these cells in order to characterize the abnormalities of this program. This study allows us to highlight the specificity of this proliferative program and to identify key genes of tumor program. These genes constitute potential new therapeutic targets
Marmiesse, Lucas. "Mathematical modelling of the transcriptional network controlled by MYB30 and MYB96, two transcription factors involved in the defence response of the model plant Arabidopsis thaliana." Thesis, Toulouse 3, 2016. http://www.theses.fr/2016TOU30278.
Full textOver the years, a lot of data has been accumulated concerning the role and regulation of MYB30 and MYB96 transcription factors during the defence responses of the plant Arabidopsis thaliana in response to pathogenic bacteria. My PhD project consisted in using mathematical modelling methods to study the role of these transcription factors on plant metabolism during infection. I developed hybrid methods capable of combining analyses of regulatory and metabolic networks. These studies showed the importance of MYB96 which seems to positively regulate many genes involved in the biosynthesis of very long chain fatty acids and their derivatives
Boukhatmi, Hadi. "Mise en place de l'identité des muscles au cours de la spécification des myoblastes chez la drosophile." Toulouse 3, 2012. http://thesesups.ups-tlse.fr/1777/.
Full textThe somatic musculature of the Drosophila embryo is a classical model to study the regulatory processes that generate cellular diversity. Muscle formation is a multistep process: the first step is the specification, within the mesoderm, of a group of competent cells, called promuscular cluster. The second step is the selection of a progenitor cell (PC) from this cluster. Asymmetric division of each PC then generates muscle founder cells (FC). Finally, each FC undergoes a fusion process with fusion competent myoblasts (FCM) to generate a muscle fiber. Each muscle is formed of a single multinucleate fiber. Each Drosophila muscle has a specific identity, as it can be distinguished by its position, shape, orientation, attachment, and innervation pattern. Muscle identity reflects the expression by each PC/FC of a specific combination of identity Transcription Factors (iTF). In the laboratory, we study the control of muscle identity, using as entry point, the expression and requirement of the iTF Collier (Col) during development of a dorso-lateral (DA3) muscle. I started my PhD by characterizing col transcriptional regulation during early steps of DA3 muscle formation. Starting from computational predictions, I identified an early col cis regulatory module (Early CRM) responsible for col activation in a promuscular cluster. A late col CRM, active from the PC stage, had previously been characterized in the laboratory. To determine with more precision the temporal windows of activity of each of these CRM, I designed a novel intron-containing reporter gene in order to detect primary transcripts. This allowed me to show that the late and the early CRMs together reproduce precisely the endogenous col expression pattern. Characterization of the early mesodermal col CRM also allowed to do lineage experiments and determine the fate of FCMs that transiently express Col at the promuscular stage. I found that these myoblasts contribute mostly to dorso-lateral muscles. During the second part of my thesis, I described a new role of the LIM-homeodomain TF Tailup/Islet1 (Tup) in specifying dorsal muscles. I first showed that Tup is specifically expressed in the four dorsal muscles. In tup null mutants, on one hand, the dorsal musculature is severely disorganized and, on the other hand, the dorsal DA2 muscle ectopically expresses Col and is transformed into a dorso-lateral DA3-like muscle. I showed that the DA2 PC is singled out from the Col promuscular cluster when cells of this cluster still express (transitorily) the homeodomain TF Tinman/Nkx2. 5 (Tin). The DA2 PC gives rise to the DA2 FC and a (dorso-lateral) adult muscle precursor (AMP). Tup activation by Tin in the DA2 PC is required to repress col and establish a DA2 instead of DA3 identity. In conclusion, my work allowed to propose a model which connects a temporal sequence of transcriptional regulation of iTFs to the specification of muscle PC identity and final muscle pattern. It provides a novel, dynamic view of how muscle identity is specified. These findings also provide novel parallels with the specification of pharyngeal muscles in vertebrates
Seyres, Denis. "Identification et analyse d'éléments cis-régulateurs impliqués dans les mécanismes de régulation transcriptionnelle des gènes au cours de la cardiogénèse chez la drosophile." Thesis, Aix-Marseille, 2015. http://www.theses.fr/2015AIXM4068.
Full textUnderstanding how gene expression is spatio-temporally regulated remains a crucial step in our understanding of organogenesis. Identification of transciptional cis-regulatory elements in a tissu-specific manner could allow to understand logical rules leading regulatory network organisation and to identify new actors (in particular transcription factors). Analysis of chromatin marks (H3K27ac and H3K4me3) specifically in cardiac cells (104 cells) during differentiation allowed the identification of transcriptional cis-regulatory regions. Via a machine learning approach, new cardiac specific regulatory regions and two transcription factors (bagpipe and hamlet) have been identified. Multiple sequence alignment of regulatory regions suggests that regions associated to H3K27ac in cardiac cells during these steps of organogenesis share a consensus sequence. These new regulatory elements integrate and complete the gene regulatory network underlying late steps of cardiogenesis
Marguet, Didier. "Analyses structurale et fonctionnelle du gène SRP de Saccharomyces cerevisiae codant pour une protéine riche en résidu sérine : étude de sa régulation transcriptionnelle positive par le glucose." Grenoble 1, 1986. http://www.theses.fr/1986GRE10036.
Full textCerutti, Franck. "Evolution et coévolution des petits ARNs régulateurs et des gènes codants chez les bactéries." Thesis, Toulouse 3, 2018. http://www.theses.fr/2018TOU30010/document.
Full textNon coding RNAs (ncRNA) are main actors of gene expression regulation and are found ubiquitously in all domains of life. In bacteria, ncRNAs play key roles in a wide range of physiological and adaptive processes. These "small non coding RNAs" (sRNAs) are identified by high-throughput experimental methods (microarray, tilling-array, ...) in several bacteria species of interest. They mainly act at post-transcriptional level through physical interactions with one or several mRNA(s). Nevertheless, the available informations about mRNA targets and sRNAs functions, remain very limited. In addition, evolutionary patterns of sRNAs have been poorly studied in pathogenic bacteria. The main hypothesis of my PhD work is therefore that analysis of evolution and coevolution between sRNAs and other functional elements in a given genomes set, may allow to understand their evolutionary histories, to better characterize their putative functions, and may also help to identify their potential mRNA(s) target(s). For this purpose, we designed and developed a robust and generic phylogenomic approach to analyze evolution and coevolution between sRNAs and mRNA from their presence-absence profiles, in a set of annotated bacterial genomes. This method was thereafter used to analyze evolution and coevolution of 154 Listeria monocytogenes EGD-e trans regulatory sRNAs in 79 complete genomes of Listeria. This approach allowed us to discover 52 accessory sRNAs, the majority ofwhich were present in the Listeria common ancestor and were subsequently lost during evolution of Listeria strains. We then detected significant coevolutions events between 23 sRNAs and 52 mRNAs and reconstructed the coevolving network of Listeria sRNA and mRNA. This network contains a main hub of 12 sRNAs that coevolves with mRNA encoding cell wall proteins and virulence factors. Among them, we have identified 4 sRNAs coevolving with 7 internalin-coding genes that are known to group important virulence factors of Listeria. Additionaly, rli133, a sRNA that coevolve with several genes involved in Listeria pathogenicity, exhibits regions compatible with direct translational inhibitory physical interactions for most of its coevolution partners
Girardot, Charles. "Deciphering enhancer activity in Drosophila based on transcription factor occupancy and chromatin state chromatin state characterization." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2012. http://tel.archives-ouvertes.fr/tel-00829472.
Full textTreffandier, Hélène. "Etude du phosphorelais RcsCDB/FA d'Escherichia coli." Toulouse 3, 2009. http://thesesups.ups-tlse.fr/797/.
Full textTwo-component systems, also called phosphorelays are the major signalling pathways in bacteria. They are widespread and mediate a large variety of adaptative cellular responses. The Rcs system of Escherichia coli is a complex phosphorelay composed of five proteins: RcsCDBFA. Exclusive to the Enterobacteriacae, the Rcs phosphorelay modulates biofilm formation and virulence in several pathogens. It is activated by membrane alterations and influences expression of 2 to 3% of the bacterial genome. However, the role of the Rcs system in adaptation to the environment remains elusive. The three objectives of my PhD were (i) to explore further the role of the Rcs system in adaptation to relevant environmental conditions (ii) to rationalize the complexity of the Rcs phosphorelay and, in particular, to explain the role of the accessory co-factor RcsA in the Rcs response (iii) to develop an integrated vision of the system through the identification of its protein partners. Within the framework of these objectives, my work proved that the Rcs system is essential for resistance to low pH, a situation encountered by E. Coli in mammals' stomach. My research also suggests that the accessory cofactor RcsA modulates the kinetics of expression of the whole RcsB regulon, in particular by prolonging the Rcs response after the phosphorelay's activating signal has stopped. To finish with, my work revealed a greater complexity in rcsA regulation than was previously thought to exist, by showing that it is twofold: transcriptional and post-transcriptional
Znaidi, Sadri. "Identification des réseaux transcriptionnnels de résistance aux antifongiques chez Candida albicans." Thèse, 2009. http://hdl.handle.net/1866/3560.
Full textMany azole resistant Candida albicans clinical isolates overexpress genes encoding azole resistance effectors that belong to two functional categories: i) CDR1, CDR2 and MDR1, encoding azole-efflux transporters and ii) ERG11, encoding the target of azoles 14-lanosterol demethylase. The constitutive overexpression of these genes is due to activating mutations in transcription factors of the zinc cluster family (Zn2Cys6) which control their expression. Tac1p (Transcriptional activator of CDR genes 1), controlling the expression of CDR1 and CDR2, Mrr1p (Multidrug resistance regulator 1), regulating MDR1 expression and Upc2p (Uptake control 2), controlling the expression of ERG11. Another determinant of clinical azole resistance is PDR16, encoding a phospholipid transferase, whose overexpression often accompanies that of CDR1 and CDR2 in clinical isolates, suggesting that the three genes belong to the same regulon, potentially that of Tac1p. Further, MDR1 expression is not only regulated by Mrr1p, but also by the basic-leucine zipper transcription factor Cap1p (Candida activator protein 1), which controls the oxidative stress response in C. albicans and whose mutation confers azole resistance via MDR1 overexpression. These observations suggest that a complex transcriptional regulatory network controls azole resistance in C. albicans. My Ph.D. studies are aimed at identifying the direct transcriptional targets of Tac1p, Upc2p and Cap1p using genetics and functional genomics approches in order to i) characterize their regulatory network and the transcriptional modules under their direct control and ii) infer their biological functions and better understand their roles in azole resistance. In the first part of my studies, I showed that Tac1p does not only control the expression of CDR1 and CDR2, but also that of PDR16. My results also identified a new activating mutation in Tac1p (N972D) and revealed that the expression of CDR1 and PDR16 is under the control of another yet unknown regulator. The combination of transcriptomics and genome-wide location (ChIP-chip) approaches allowed me to identify the in vivo direct targets of Tac1p (PDR16, CDR1, CDR2, ERG2, others), Upc2p (ERG11, ERG2, MDR1, CDR1, others) and Cap1p (MDR1, GCY1, GLR1, others). These results also revealed that Upc2p does not only control the expression of ERG11 but also that of MDR1 and CDR1. Many new functional features of these transcription factors were found, including the constitutive binding of Tac1p to its targets under both activating and non-activating conditions, and the binding of Cap1p which extends beyond the promoter region of its target genes, to cover the open reading frame and the putative transcription termination regions, suggesting a physical interaction with the transcriptional machinery. The characterization of the transcriptional regulatory network revealed a functional interaction between these factors, notably between Cap1p and Mrr1p, and inferred potential biological functions for Tac1p (lipid mobilization and traffic, response to oxidative and osmotic stress) and confirmed or suggested other functions for Upc2p (sterol metabolism) and Cap1p (oxidative stress response, regulation of nitrogen utilization and phospholipids transport). Taken together, my results suggest that azole resistance in C. albicans is tightly linked to membrane lipid metabolism and oxidative stress response.
Deneault, Eric. "Activité des cellules souches : identification de nouveaux effecteurs dans le système hématopoïétique." Thèse, 2012. http://hdl.handle.net/1866/9002.
Full textSomatic stem cells usually exhibit a very different behavior compared to pluripotent stem cells. The molecular basis of embryonic stem cell self-renewal was recently decrypted by the relative straightforwardness with which we can now purify and maintain these cells in culture for long periods of time. However, this is not the case with hematopoietic stem cells. In order to elucidate the molecular mechanisms of hematopoietic stem cell self-renewal, I developed a novel gain-of-function screening strategy, which bypasses some constraints found with these cells. Starting from a list of more than 700 candidate nuclear factors and asymmetric division factors, I have identified 24 new factors that increase hematopoietic stem cell activity when overexpressed. I have also found that nine of these factors act extrinsically to hematopoietic stem cells, i.e., the effect comes from the engineered feeder cells in co-culture. Moreover, I have revealed a new transcriptional regulatory network including five of the factors identified, i.e., PRDM16, SPI1, KLF10, FOS and TFEC. This network is particularly similar to that involved in osteoclastogenesis. These results raise the hypothesis that osteoclasts might also be part of the functional hematopoietic stem cell niche in the bone marrow. Furthermore, I have identified a second regulatory network involving SOX4, SMARCC1 and several factors previously identified in the laboratory, i.e., BMI1, MSI2 and KDM5B. Besides, several lines of evidence tend to show that there are fundamental differences between mouse and human hematopoietic stem cells.
Al-Khoury, Racha. "Systematic analysis of protein complexes involved in the human RNA polymerase II machinery." Thèse, 2009. http://hdl.handle.net/1866/2930.
Full textGenomes encode most of the functions necessary for cell growth and differentiation. Gene transcription, RNA processing, and chromatin remodeling are central processes in the interpretation of the information contained in genomic DNA. Although many protein complexes forming the cellular machinery that interprets mammalian genomes have been studied, a number of additional complexes remain to be identified and characterized. Using proteomic approaches, Dr. Benoit Coulombe’s laboratory purified many components of the RNAPII transcription machinery using tandem affinity purification (TAP), a procedure that allows the isolation of protein complexes as they likely exist in live mammalian cells, and the identification of interaction partners using mass spectrometry. High confidence interactions were selected computationally and used to draw the map of a network connecting many components of the mRNA transcriptional machinery. By applying this procedure, our lab has identified, for the first time, a group of proteins, that interacts both physically and functionally with human RNAPII, and whose properties suggest a role in the assembly of multi-subunit complexes, acting as RNAPII-specific scaffolding proteins and chaperones. The aim of my project was to continue the characterization of the network of protein complexes involving transcription factors, and thus, further pursuing our survey of protein complexes in whole cell extracts. Eight novel RNAPII interaction partners (PIH1D1, GPN3, WDR92, PFDN2, KIAA0406, PDRG1, CCT4 and CCT5) were purified using the tandem affinity purification (TAP) method, and their interaction partners were identified by mass spectrometry. Over the years, our lab’s analysis of transcriptional regulation and mechanisms has contributed novel and important knowledge that provided better understanding of mRNA synthesis. This knowledge is paramount to the development of therapeutics that will target transcriptional mechanisms.