Academic literature on the topic 'Facteur de transcription CHOP'
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Journal articles on the topic "Facteur de transcription CHOP"
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Chiribau, Calin-Bogdan, Francesca Gaccioli, Charlie C. Huang, Celvie L. Yuan, and Maria Hatzoglou. "Molecular Symbiosis of CHOP and C/EBPβ Isoform LIP Contributes to Endoplasmic Reticulum Stress-Induced Apoptosis." Molecular and Cellular Biology 30, no. 14 (May 17, 2010): 3722–31. http://dx.doi.org/10.1128/mcb.01507-09.
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ABSTRACT Induction of the transcription factor CHOP (CCAAT-binding homologous protein; GADD 153) is a critical cellular response for the transcriptional control of endoplasmic reticulum (ER) stress-induced apoptosis. Upon nuclear translocation, CHOP upregulates the transcription of proapoptotic factors and downregulates antiapoptotic genes. Transcriptional activation by CHOP involves heterodimerization with other members of the basic leucine zipper transcription factor (bZIP) family. We show that the bZIP protein C/EBPβ isoform LIP is required for nuclear translocation of CHOP during ER stress. In early ER stress, LIP undergoes proteasomal degradation in the cytoplasmic compartment. During later ER stress, LIP binds CHOP in both cytoplasmic and nuclear compartments and contributes to its nuclear import. By using CHOP-deficient cells and transfections of LIP-expressing vectors in C/EBPβ−/− mouse embryonic fibroblasts (MEFs), we show that the LIP-CHOP interaction has a stabilizing role for LIP. At the same time, CHOP uses LIP as a vehicle for nuclear import. LIP-expressing C/EBPβ−/− MEFs showed enhanced ER stress-induced apoptosis compared to C/EBPβ-null cells, a finding in agreement with the decreased levels of Bcl-2, a known transcriptional control target of CHOP. In view of the positive effect of CHOP-LIP interaction in mediating their proapoptotic functions, we propose this functional cooperativity as molecular symbiosis between proteins.
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Teske, Brian F., Michael E. Fusakio, Donghui Zhou, Jixiu Shan, Jeanette N. McClintick, Michael S. Kilberg, and Ronald C. Wek. "CHOP induces activating transcription factor 5 (ATF5) to trigger apoptosis in response to perturbations in protein homeostasis." Molecular Biology of the Cell 24, no. 15 (August 2013): 2477–90. http://dx.doi.org/10.1091/mbc.e13-01-0067.
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Environmental stresses that disrupt protein homeostasis induce phosphorylation of eIF2, triggering repression of global protein synthesis coincident with preferential translation of ATF4, a transcriptional activator of the integrated stress response (ISR). Depending on the extent of protein disruption, ATF4 may not be able to restore proteostatic control and instead switches to a terminal outcome that features elevated expression of the transcription factor CHOP (GADD153/DDIT3). The focus of this study is to define the mechanisms by which CHOP directs gene regulatory networks that determine cell fate. We find that in response to proteasome inhibition, CHOP enhances the expression of a collection of genes encoding transcription regulators, including ATF5, which is preferentially translated during eIF2 phosphorylation. Transcriptional expression of ATF5 is directly induced by both CHOP and ATF4. Knockdown of ATF5 increases cell survival in response to proteasome inhibition, supporting the idea that both ATF5 and CHOP have proapoptotic functions. Transcriptome analysis of ATF5-dependent genes reveals targets involved in apoptosis, including NOXA, which is important for inducing cell death during proteasome inhibition. This study suggests that the ISR features a feedforward loop of stress-induced transcriptional regulators, each subject to transcriptional and translational control, which can switch cell fate toward apoptosis.
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Ubeda, Mariano, and Joel F. Habener. "CHOP Transcription Factor Phosphorylation by Casein Kinase 2 Inhibits Transcriptional Activation." Journal of Biological Chemistry 278, no. 42 (July 21, 2003): 40514–20. http://dx.doi.org/10.1074/jbc.m306404200.
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Cazanave, Sophie C., Nafisa A. Elmi, Yuko Akazawa, Steven F. Bronk, Justin L. Mott, and Gregory J. Gores. "CHOP and AP-1 cooperatively mediate PUMA expression during lipoapoptosis." American Journal of Physiology-Gastrointestinal and Liver Physiology 299, no. 1 (July 2010): G236—G243. http://dx.doi.org/10.1152/ajpgi.00091.2010.
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Endoplasmic reticulum (ER) stress-mediated apoptosis is a key feature of hepatocyte cytotoxicity by saturated free fatty acids (FFA). This lipoapoptosis is dependent, in part, on the transcriptional upregulation of the BH3-only protein PUMA (p53 upregulated modulator of apoptosis). Although the activator protein (AP)-1 complex facilitates PUMA expression by saturated FFA, the transcription factor CAAT/enhancer binding homologous protein (CHOP) is also induced by ER stress and promotes apoptosis. To integrate the role of these two transcription factors in ER stress-induced apoptosis, we examined the relative contribution of CHOP and AP-1 in mediating PUMA induction by saturated FFA. Our results demonstrate that short-hairpin RNA-targeted knockdown of CHOP attenuates palmitate-induced apoptosis in Huh-7 cells. Loss of CHOP induction also reduced the increase in PUMA mRNA and protein levels as well as Bax activation by palmitate. No functional CHOP binding sites were identified in the PUMA promoter sequence. Rather, we observed that CHOP physically interacts with the AP-1 complex protein c-Jun upon palmitate treatment, and a CHOP:phosphorylated c-Jun heteromeric complex binds to the AP-1 consensus binding sequence within the PUMA promoter region. Finally, loss of function studies suggest that both transcription factors are necessary for maximal PUMA induction. Collectively, these data suggest that CHOP and AP-1 cooperatively mediate PUMA induction during hepatocyte lipoapoptosis.
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Bruhat, Alain, Céline Jousse, Valérie Carraro, Andreas M. Reimold, Marc Ferrara, and Pierre Fafournoux. "Amino Acids Control Mammalian Gene Transcription: Activating Transcription Factor 2 Is Essential for the Amino Acid Responsiveness of the CHOP Promoter." Molecular and Cellular Biology 20, no. 19 (October 1, 2000): 7192–204. http://dx.doi.org/10.1128/mcb.20.19.7192-7204.2000.
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ABSTRACT In mammals, plasma concentration of amino acids is affected by nutritional or pathological conditions. It has been well established that nutrients, and particularly amino acids, are involved in the control of gene expression. Here we examined the molecular mechanisms involved in the regulation ofCHOP (a CCAAT/enhancer-binding protein [C/EBP]-related gene) expression upon amino acid limitation. We have previously shown that regulation of CHOP mRNA expression by amino acid concentration has both transcriptional and posttranscriptional components. We report the analysis ofcis- and trans-acting elements involved in the transcriptional activation of the human CHOPgene by leucine starvation. Using a transient expression assay, we show that a cis-positive element is essential for amino acid regulation of the CHOP promoter. This sequence is the first described that can regulate a basal promoter in response to starvation for several individual amino acids and therefore can be called an amino acid response element (AARE). In addition, we show that the CHOP AARE is related to C/EBP and ATF/CRE binding sites and binds in vitro the activating transcription factor 2 (ATF-2) in starved and unstarved conditions. Using ATF-2-deficient mouse embryonic fibroblasts and an ATF-2-dominant negative mutant, we demonstrate that expression of this transcription factor is essential for the transcriptional activation of CHOP by leucine starvation. Altogether, these results suggest that ATF-2 may be a member of a cascade of molecular events by which the cellular concentration of amino acids can regulate mammalian gene expression.
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Ubeda, Mariano, Mario Vallejo, and Joel F. Habener. "CHOP Enhancement of Gene Transcription by Interactions with Jun/Fos AP-1 Complex Proteins." Molecular and Cellular Biology 19, no. 11 (November 1, 1999): 7589–99. http://dx.doi.org/10.1128/mcb.19.11.7589.
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ABSTRACT The transcription factor CHOP (C/EBP homologous protein 10) is a bZIP protein induced by a variety of stimuli that evoke cellular stress responses and has been shown to arrest cell growth and to promote programmed cell death. CHOP cannot form homodimers but forms stable heterodimers with the C/EBP family of activating transcription factors. Although initially characterized as a dominant negative inhibitor of C/EBPs in the activation of gene transcription, CHOP-C/EBP can activate certain target genes. Here we show that CHOP interacts with members of the immediate-early response, growth-promoting AP-1 transcription factor family, JunD, c-Jun, and c-Fos, to activate promoter elements in the somatostatin, JunD, and collagenase genes. The leucine zipper dimerization domain is required for interactions with AP-1 proteins and transactivation of transcription. Analyses by electrophoretic mobility shift assays and by an in vivo mammalian two-hybrid system for protein-protein interactions indicate that CHOP interacts with AP-1 proteins inside cells and suggest that it is recruited to the AP-1 complex by a tethering mechanism rather than by direct binding of DNA. Thus, CHOP not only is a negative or a positive regulator of C/EBP target genes but also, when tethered to AP-1 factors, can activate AP-1 target genes. These findings establish the existence of a new mechanism by which CHOP regulates gene expression when cells are exposed to cellular stress.
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Yoshida, Hiderou, Tetsuya Okada, Kyosuke Haze, Hideki Yanagi, Takashi Yura, Manabu Negishi, and Kazutoshi Mori. "ATF6 Activated by Proteolysis Binds in the Presence of NF-Y (CBF) Directly to the cis-Acting Element Responsible for the Mammalian Unfolded Protein Response." Molecular and Cellular Biology 20, no. 18 (September 15, 2000): 6755–67. http://dx.doi.org/10.1128/mcb.20.18.6755-6767.2000.
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ABSTRACT Transcription of genes encoding molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) is induced by accumulation of unfolded proteins in the ER. This intracellular signaling, known as the unfolded protein response (UPR), is mediated by thecis-acting ER stress response element (ERSE) in mammals. In addition to ER chaperones, the mammalian transcription factor CHOP (also called GADD153) is induced by ER stress. We report here that the transcription factor XBP-1 (also called TREB5) is also induced by ER stress and that induction of CHOP and XBP-1 is mediated by ERSE. The ERSE consensus sequence is CCAAT-N9-CCACG. As the general transcription factor NF-Y (also known as CBF) binds to CCAAT, CCACG is considered to provide specificity in the mammalian UPR. We recently found that the basic leucine zipper protein ATF6 isolated as a CCACG-binding protein is synthesized as a transmembrane protein in the ER, and ER stress-induced proteolysis produces a soluble form of ATF6 that translocates into the nucleus. We report here that overexpression of soluble ATF6 activates transcription of the CHOP and XBP-1 genes as well as of ER chaperone genes constitutively, whereas overexpression of a dominant negative mutant of ATF6 blocks the induction by ER stress. Furthermore, we demonstrated that soluble ATF6 binds directly to CCACG only when CCAAT exactly 9 bp upstream of CCACG is bound to NF-Y. Based on these and other findings, we concluded that specific and direct interactions between ATF6 and ERSE are critical for transcriptional induction not only of ER chaperones but also of CHOP and XBP-1.
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Ubeda, M., X. Z. Wang, H. Zinszner, I. Wu, J. F. Habener, and D. Ron. "Stress-induced binding of the transcriptional factor CHOP to a novel DNA control element." Molecular and Cellular Biology 16, no. 4 (April 1996): 1479–89. http://dx.doi.org/10.1128/mcb.16.4.1479.
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CHOP (GADD153) is a mammalian nuclear protein that dimerizes with members of the C/EBP family of transcriptional factors. Absent under normal conditions, CHOP is induced by the stress encountered during nutrient deprivation, the acute-phase response, and treatment of cells with certain toxins. The basic region of CHOP deviates considerably in sequence from that of other C/EBP proteins, and CHOP-C/EBP heterodimers are incapable of binding to a common class of C/EBP sites. With respect to such sites, CHOP serves as an inhibitor of the activity of C/EBP proteins. However, recent studies indicate that certain functions of CHOP, such as the induction of growth arrest by overexpression of the wild-type protein and oncogenic transformation by the TLS-CHOP fusion protein, require an intact basic region, suggesting that DNA binding by CHOP may be implicated in these activities. In this study an in vitro PCR-based selection assay was used to identify sequences bound by CHOP-C/EBP dimers. These sequences were found to contain a unique core element PuPuPuTGCAAT(A/C)CCC. Competition in DNA-binding assays, DNase 1 footprint analysis, and methylation interference demonstrate that the binding is sequence specific. Deletions in the basic region of CHOP lead to a loss of DNA binding, suggesting that CHOP participates in this process. Stress induction in NIH 3T3 cells leads to the appearance of CHOP-containing DNA-binding activity. CHOP is found to contain a transcriptional activation domain which is inducible by cellular stress, lending further support to the notion that the protein can function as a positively acting transcription factor. We conclude that CHOP may serve a dual role both as an inhibitor of the ability of C/EBP proteins to activate some target genes and as a direct activator of others.
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Wan, Xiao-shan, Xiang-hong Lu, Ye-cheng Xiao, Yuan Lin, Hong Zhu, Ting Ding, Ying Yang, et al. "ATF4- and CHOP-Dependent Induction of FGF21 through Endoplasmic Reticulum Stress." BioMed Research International 2014 (2014): 1–9. http://dx.doi.org/10.1155/2014/807874.
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Fibroblast growth factor 21 (FGF21) is an important endogenous regulator involved in the regulation of glucose and lipid metabolism. FGF21 expression is strongly induced in animal and human subjects with metabolic diseases, but little is known about the molecular mechanism. Endoplasmic reticulum (ER) stress plays an essential role in metabolic homeostasis and is observed in numerous pathological processes, including type 2 diabetes, overweight, nonalcoholic fatty liver disease (NAFLD). In this study, we investigate the correlation between the expression of FGF21 and ER stress. We demonstrated that TG-induced ER stress directly regulated the expression and secretion of FGF21 in a dose- and time-dependent manner. FGF21 is the target gene for activating transcription factor 4 (ATF4) and CCAAT enhancer binding protein homologous protein (CHOP). Suppression of CHOP impaired the transcriptional activation of FGF21 by TG-induced ER stress in CHOP−/− mouse primary hepatocytes (MPH), and overexpression of ATF4 and CHOP resulted in FGF21 promoter activation to initiate the transcriptional programme. In mRNA stability assay, we indicated that ER stress increased the half-life of mRNA of FGF21 significantly. In conclusion, FGF21 expression is regulated by ER stress via ATF- and CHOP-dependent transcriptional mechanism and posttranscriptional mechanism, respectively.
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Netherton, Christopher L., James C. Parsley, and Thomas Wileman. "African Swine Fever Virus Inhibits Induction of the Stress-Induced Proapoptotic Transcription Factor CHOP/GADD153." Journal of Virology 78, no. 19 (October 1, 2004): 10825–28. http://dx.doi.org/10.1128/jvi.78.19.10825-10828.2004.
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ABSTRACT Stress signaling from mitochondria and the endoplasmic reticulum (ER) leads to the induction of the proapoptotic transcription factor CHOP/GADD153. Many viruses use the ER as a site of replication and/or envelopment, and this activity can lead to the activation of ER stress and apoptosis. African swine fever virus (ASFV) is assembled on the cytoplasmic face of the ER and ultimately enveloped by ER membrane cisternae. The virus also recruits mitochondria to sites of viral replication and induces the mitochondrial stress protein hsp60. Here we studied the effects of ASFV on the induction of CHOP/GADD153 in infected cells. Interestingly, unlike other ER-tropic viruses, ASFV did not activate CHOP and was able to inhibit the induction of CHOP/GADD153 by a number of exogenous stimuli.
Dissertations / Theses on the topic "Facteur de transcription CHOP"
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Loinard, Céline. "Rôle des facteurs de transcription HIF et CHOP-10 dans le processus de néovascularisation post-ischémique." Paris 5, 2009. http://www.theses.fr/2009PA05P640.
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Le développement de stratégie thérapeutique stimulant la formation de nouveaux vaisseaux reste un challenge clinique majeur dans le traitement des pathologies ischémiques. Nous avons mis en évidence le potentiel thérapeutique du «silencing» des prolines hydroxylases (PHD), par shRNA, au niveau du territoire ischémique dans un contexte nondiab et diab. Cette inhibition spécifique et transitoire de la PHD ciblée se traduit par une forte augmentation de HIF-1a, VEGF, NOSe et également par une amplification du recrutement des macrophages dans le muscle ischémié stimulant ainsi le processus de néovascularisation. Finalement, la co-administration de shHIF-1a et shPHD3 abroge les effets induits par shPHD3 démontrant ainsi que l’activation de HIF-1a soustend la néovascularisation. Ces travaux démontrent que l’inhibition des PHD peut être considéré comme une nouvelle stratégie de néovascularisation thérapeutique. Nous avons également montré que CHOP-10 inhibe le processus de néovascularisation post-ischémique et le potentiel pro-angiogénique des BM-MNC. CHOP-10 est fortement augmenté après l’ischémie et l’induction du diabète dans le muscle et les BM-MNC. Les souris KO CHOP-10 nondiab et diab présentent une augmentation de la NOSe et une réduction du nombre de cellules apoptotiques dans le muscle ischémique et les BM-MNC, qui se traduit par une augmentation du processus de néovascularisation. In vitro, nous démontrons que CHOP-10 régule négativement le promoteur de la NOSe. D’ailleurs les souris invalidées pour CHOP-10 et NOSe présentent un déficit de néovaisseaux dans le territoire ischémique. Cette étude identifie le facteur de transcription CHOP-10 comme un important modulateur de la formation et de la maturation des vaisseauxTherapeutic angiogenesis is viewed as a highly promising strategy to ensure revascularization of ischemic tissues by promoting the growth of new vessels or the maturation of pre-existing ones. First, we investigated whether inhibition of PHD via upregulating HIF might promote post-ischemic neovascularization. PHDs silencing induced a specific and transient downregulation of their respective mRNA and protein levels and as expected upregulated HIF-1a. As a consequence levels of pro-angiogenic and pro-arteriogenic actors were enhanced leading to activation of post-ischemic inflammatory response and neovascularization. Of interest, co-administration of shHIF-1a with shPHD3 abrogated shPHD3-related effects suggesting that activation of HIF-1a-dependent pathways mediated the pro-angiogenic effects of PHD silencing. Inhibition of PHD activated endogenous HIF-a signaling and subsequently promoted post-ischemic neovascularization. Second, we analyzed the role of CHOP-10 in postnatal neovascularization. In skeletal muscle and BM-MNC, CHOP-10 was upregulated by ischemia and diabetes. Neovascularization process was increased in nondiab and diab CHOP-10 KO mice. This effect was associated with a reduction in the number of apoptotic cells and an upregulation of eNOS levels. In line with these results, overexpression of CHOP-10 inhibited basal transcriptional activation of the eNOS promoter. Interestingly, enhanced post-ischemic neovascularization in CHOP-10 KO was fully blunted in CHOP-10/eNOS KO mice. This study identifies CHOP-10 as an important transcription factor modulating vessel formation and maturation
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Carrière-Pazat, Audrey. "Les espèces actives de l'oxygène d'origine mitochondriale : un élément clé dans le contrôle du développement du tissu adipeux blanc." Toulouse 3, 2005. http://www.theses.fr/2005TOU30003.
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La mitochondrie est un des sites majeurs de la production d'espèces actives de l'oxygène (EAOs). Les EAOs participent au contrôle du devenir cellulaire et agissent comme de véritables seconds messagers. Le but de notre travail a été de démontrer l'implication des EAOs mitochondriales dans le contrôle du développement du tissu adipeux blanc. A l'aide d'approches pharmacologiques, nous avons démontré que les EAOs mitochondriales contrôlent la prolifération des précurseurs adipocytaires ainsi que leur différenciation en adipocytes. Le facteur de transcription CHOP-10 est une cible critique des EAOs mitochondriales et pourrait jouer un rôle clé dans l'inhibition de la différenciation. Cette voie de signalisation EAOs mitochondriales/CHOP-10 est en partie responsable des effets de l'hypoxie sur la différenciation adipocytaire. Ces résultats démontrent que la production d'EAOs mitochondriales doit être considérée comme un élément de contrôle dans le développement du tissu adipeux blancMitochondria are the main site of reactive oxygen species (ROS) generation. When moderately produced, they function as physiological signaling molecules. The present study therefore tested the implication of mitochondrial ROS in the control of white adipose tissue development. Pharmacological manipulations of mitochondrial ROS generation demonstrate that they negatively control preadipocyte proliferation and also their differentiation into adipocytes. Moreover, the transcription factor CHOP-10 is a specific target of mitochondrial ROS and could be responsible for their effects on adipocyte differentiation. This signaling pathway involving mitochondrial ROS and CHOP-10 triggers hypoxia dependent effects on adipocyte differentiation. Taken together, these data demonstrate that mitochondrial ROS should be considered as antiadipogenic signaling molecules
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Manuel, Martine. "Recherche des cibles du facteur HSF2 chez la souris." Paris 7, 2002. http://www.theses.fr/2002PA077115.
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Maurel, Sébastien. "Rôle des protéines de choc thermique dans la régulation du facteur de transcription HIF." Phd thesis, Université de Bourgogne, 2011. http://tel.archives-ouvertes.fr/tel-00704624.
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HIF1α et HIF2α sont des protéines largement impliquées dans le développement de pathologies posant des problèmes majeurs de santé publique, comme le cancer. Leur activité, qui est régulée prioritairement par leur stabilité via le système ubiquitine-protéasome, coordonne de nombreux processus cellulaires susceptibles de favoriser le développement de ces maladies. Un enjeu récent de la recherche thérapeutique est d'identifier des partenaires protéiques pouvant réguler les protéines HIFα, afin de mettre au point des thérapies ciblées. Les protéines de choc thermique (HSPs) sont une classe de protéines dont une des fonctions essentielles est de réguler l'homéostasie protéique dans la cellule, en interagissant avec le protéasome. Certaines d'entre elles, HSP27 et HSP90, ont la faculté de pouvoir réguler spécifiquement la stabilité de nombreuses protéines souvent elles-mêmes impliquées dans l'apparition de ces pathologies. L'objectif de ce travail était de savoir si ces deux HSPs peuvent contrôler la stabilité de la protéine HIF2α. Nos résultats suggèrent qu'HSP27 pourrait stimuler la dégradation de HIF2α en favorisant son ubiquitination. Ce résultat est surprenant, en raison du rôle connu d'HSP27 dans la progression tumorale. Il est donc nécessaire de le confirmer et d'en préciser les processus biologiques sous-jacents. D'autre part, nos autres résultats semblent confirmer qu'HIF2α est une protéine cliente d'HSP90. De plus, nous montrons pour la première fois que l'inhibition d'HSP90 par le 17-DMAG diminue la production de VEGF dépendante de HIF2α. Des travaux récents suggèrent qu'HIF2α a un rôle prédominant dans la progression tumorale, et peut constituer une cible globale de choix dans plusieurs types de cancer. Il conviendrait d'évaluer la capacité des inhibiteurs d'HSP90 à supprimer des fonctions de HIF2α nouvellement décrites, comme son rôle dans la maintenance des cellules souches cancéreuses.
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Samuel, Alexander. "Étude génomique des fonctions du facteur de transcription Otx2 dans la rétine de souris adulte." Phd thesis, Université Nice Sophia Antipolis, 2013. http://tel.archives-ouvertes.fr/tel-00933785.
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Pour comprendre comment les gènes du développement exercent de multiples fonctions temporelles, nous prenons comme modèle le facteur de transcription Otx2. Celui-ci est impliqué dans la gastrulation, le développement de l'œil, du système olfactif, de la glande pinéale, du thalamus et de la région cranio-faciale. Dans la rétine adulte, deux tissus distincts expriment Otx2 : l'épithélium pigmenté (RPE) et la rétine neurale, contenant les photorécepteurs. L'ablation globale du gène Otx2 entraîne la dégénérescence exclusive des photorécepteurs alors qu'elle modifie l'expression de gènes surtout dans le RPE. Ces faits suggèrent un mécanisme non autonome, confirmé par des expériences de gain et perte de fonction restreintes au RPE. Pour approcher les fonctions de la protéine Otx2 dans la rétine neurale et le RPE, une étude à grande échelle de ses cibles génomiques a été menée. Les profils distincts d'occupation du génome du RPE et de la rétine neurale suggèrent des fonctions différentes d'Otx2. Dans la rétine neurale, ce profil est très proche de celui du facteur paralogue Crx, indiquant une redondance fonctionnelle entre Otx2 et Crx. Nous avons émis l'hypothèse qu'une combinatoire de partenaires protéiques différents permet de moduler l'action d'Otx2 en sélectionnant des cibles génomiques distinctes. Pour identifier cette combinatoire in vivo et la corréler aux fonctions exercées par Otx2, nous avons créé une lignée de souris exprimant une protéine de fusion Otx2-TAP-tag à un niveau physiologique. Cet outil permettra la purification des complexes protéiques Otx2 in vivo et leur identification par analyse protéomique.
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Lucas, Alexandre. "GADD45 gamma régule la mort des cellules cardiaques et le remodelage post-infarctus du myocarde." Thesis, Toulouse 3, 2016. http://www.theses.fr/2016TOU30404.
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Le remodelage du ventricule gauche cardiaque post-infarctus est multifactoriel et bien connu. Il est caractérisé par un changement électrophysiologique, une fibrose et une mort des cellules cardiaques. La voie des Mitogen-activated protein kinase (MAPK) et plus particulièrement l'activation de la p38 MAPK est connue pour influencer ses processus et mener à l'insuffisance cardiaque (IC). La Growth arrest and DNA-damage-inducible 45 (GADD45) est capable d'interagir et de réguler la p38 MAPK. GADD45 a des effets pléiotropiques mais son rôle dans le cœur est encore peu caractérisé. D'après la littérature, les différentes isoformes de GADD45 sont différentiellement exprimées lors d'une cardiomyopathie. Ici, nous avons tout d'abord identifié l'isoforme de GADD45 impliquée lors de l'infarctus du myocarde (IDM) de souris, GADD45ƴ, puis nous avons étudié son impact dans les phases précoces et tardives du développement d'une IC après un IDM. Pour cela nous avons injecté en intraveineuse un vecteur adeno-associated viral (AAV9) codant GADD45 ƴ sous le contrôle du promoteur à la cardiac Troponin T (cTnT). Cette surexpression, mimant la dérégulation de GADD45 ƴ lors d'un IDM, a entrainé une augmentation de la fibrose, de l'apoptose et une dysfonction cardiaque de ces souris menant à une IC. De plus, un KO de GADD45 ƴ a permis de protéger ces souris de lésions dûes à l'ischémie, notamment par une réduction de l'apoptose des cardiomyocytes. Nous démontrons enfin que les mécanismes permettant cette protection mettent en jeu l'activation de la receptor-interacting protein kinase 1 (RIP1) et de la caspase 8 par GADD45 ƴ sous le contrôle de la p38 MAPK. Notre travaille démontre donc que l'accumulation de GADD45 ƴ lors de l'IDM est un élément important dans le développement de l'IC en induisant une apoptose dépendante de la p38 MAPK. Ce travail permet d'envisager GADD45 ƴ comme une cible thérapeutique potentielle de l'ICLeft ventricular post-infarction remodelling is multifactorial and well-known. It is characterized by an electrophysiological change, a fibrosis and a death of the cardiac cells. Mitogen-activated protein kinase (MAPK) pathway and more particularly the activation of p38 MAPK are known to influence its processes and to lead to heart failure (HF). Growth arrest and DNA-damage-inducible 45 (GADD45) is able to interact and control p38 MAPK. GADD45 has pleiotropic effects but its role in the heart is little known. According to the literature, GADD45 isoforms are differentially expressed during a cardiomyopathy. Here, we first to identify the GADD45 isoform who upregulated during myocardial infarction (MI) of mouse, GADD45ƴ, then we studied his impact to the acute and late phases of the development of HF after MI. Intravenous injection of an adeno-associated viral (AAV9) vector encoding GADD45 ƴ under the control of cardiac Troponin T (cTnT) promoter. This surexpression, miming the deregulation of GADD45 ƴ during MI, cause an increase in the fibrosis, apoptose and a cardiac dysfonction of these mice leading to HF. Moreover, KO of GADD45 confers resistance to ischaemic injury, in particular by limiting cardiomyocyte apoptosis. We show finally that the mechanisms allowing this protection involves activation of the receptor-interacting protein kinase 1 (RIP1) and caspase 8 by GADD45 ƴ in a p38 MAPK dependant manner. Our works thus shows that GADD45 ƴ accumulation during MI is a significant component in HF development by inducing cardiomyocyte apoptosis in a p38 MAPK dependant manner. This work identify GADD45 ƴ as a potential therapeutic target in the development of HF
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Sakakini, Nathalie. "Rôle du facteur de transcription EGR1 dans le contrôle de l' autorenouvellement des cellules souches de glioblastomes." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM4071.
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Le glioblastome est la tumeur cérébrale de mauvais pronostic la plus fréquente et la plus agressive. Les traitements actuels combinent la chirurgie à la radio thérapie et la chimiothérapie. Cependant ces traitements sont peu efficaces. Le taux de récidive est élevé et la survie moyenne est de 15 mois.La récidive s'explique en partie par la présence de cellules initiatrices de glioblastomes (CIG). Ces cellules possèdent des propriétés de cellules souches adultes. Elles s'auto-renouvellent en maintenant un pool de cellules tumorales et se différencient en différents types cellulaires. Elles sont aussi résistantes aux thérapies par l'activation de mécanismes d'élimination des molécules destinées à les détruire. L'engagement des CIGs vers un état tumoral différencié diminue fortement leur potentiel tumorigénique les rendant plus vulnérables.Le facteur de transcription EGR1 est impliqué dans des processus biologiques comme la prolifération et la différenciation. Dans les CIG l'expression d'EGR1 est anormalement élevée. Ce niveau diminue lorsque les cellules se différencient. L'expression d'EGR1 est donc corrélée avec un état souche suggérant sa contribution dans la régulation de la prolifération des CIG ou dans le maintien de cet état.Mon objectif est de caractériser le rôle d'EGR1 dans la régulation de l'état proliférant des CIG.Nous avons démontré l'implication d'EGR1 dans une cascade de régulation impliquant le mir18a* et les gènes SHH et GLI1. Il contribue ainsi à l'autorenouvellement, à la prolifération et au maintien de l'état souche des CiGs. De plus en régulant directement le gène PDGFa, EGR1 entretient ce système régulatoire par une deuxième boucle moléculaireGlioblastoma is the most commun and agressive cerebral tumor. The current treatments combine surgery with chemotherapy and radiotherapy. However these treatments are poor effective. The relapse is frequent and the rate survival is less than 18 months.The relapse is in part due to the presence of glioblastoma initiating cells (GIC). The cells have stem cell properties. They can self-renew to maintain a pool of tumor cells and they can differentiate in different kind of tumor cells. They are also able to resist to the therapies by activating mechanisms of drug efflux. The commitment of GIC toward a differentiated tumor state decreases strongly their tumorigenic potential.EGR1 transcription factor is involved in many biological processes such as proliferation and differentiation. In the GIC EGR1 expression is abnormally elevated. This level decreases when cells are differentiated. EGR1 expression is strongly correlated with stem state suggesting its contribution in the proliferation regulation of GIC or in the maintenance of this state.My aim is to characterize the role of EGR1 in the regulation of proliferating state of the GIC.We have demonstrated the involvement of EGR1 in the pathway involving the mir18a* and the genes SHH and GLI1. It contributes so to the self-renewal, to the proliferation and to the maintenance of the stem state of GIC. In addition by directly regulating the gene PDGFa EGR1 maintains this system by a second molecular loop
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Lakhal, Wassim. "Etude fonctionnelle de trois facteurs de transcription impliqués dans la formation de la paroi secondaire chez le peuplier." Thesis, Orléans, 2013. http://www.theses.fr/2013ORLE2067/document.
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Les facteurs de transcription (FT) de la famille R2R3-MYB chez les plantes jouent un rôle important dans la formation de la paroi secondaire des cellules de bois, que ce soit en activant ou en réprimant leurs gènes cibles au sein d’un réseau régulationnel complexe. Dans ce travail, nous avons utilisé la transgénèse et l’immunoprécipitation de chromatine associée à un séquençage haut-débit (ChIP-SEQ) pour déterminer la fonction de 3 FT R2R3-MYB chez le peuplier. Les peupliers surexprimant MYB090 ont des rayons moins lignifiés ; les tiges présentent une réduction de croissance et de teneurs en lignines. MYB090 régule ses cibles à l’aide d’un motif très conservé, similaire au motif Gamyb. Ses cibles sont impliquées notamment dans la biosynthèse des lignines, cellulose et xylanes, constituants principaux des parois. Les plantes surexprimant MYB221-SRDX et MYB156 présentent une nette réduction de la lignification des parois de leurs fibres, associée à une réduction de croissance. MYB221 semble avoir pour cibles des gènes codant pour des enzymes du métabolisme, ainsi qu’un autre FT de type R2R3-MYB, dont la régulation passe par un motif conservé de type SMRE (Secondary wall MYB-Responsive Element). En conclusion, la combinaison des approches ChIP-SEQ et de transgénèse montre que MYB090 semble être un répresseur transcriptionnel de la lignification, notamment dans les rayons, et de la formation de la paroi secondaire. De même, MYB156 et MYB221 seraient également des répresseurs de la lignification, dans les fibres et les rayons. Cette thèse ouvre des perspectives sur l’établissement de réseaux de régulation transcriptionnelle de la formation de la paroi secondairePlant R2R3-MYB transcription factors (TF) play an important role in secondary cell wall formation in wood cells, by activating or repressing their target genes within a complex regulatory network. Here, we used genetic engineering and chromatin immunoprecipitation technique, associated to next-generation sequencing (ChIP-SEQ) to determine the function of 3 R2R3-MYB TF in poplar. Plants overexpressing MYB090 had less lignified parenchyma rays. The stem growth and total lignin content were reduced. MYB090 regulates target genes through a highly conserved motif, similar to Gamyb. Its target genes are involved in lignin, cellulose and xylan biosynthesis, which are the major components of secondary cell wall. Poplars overexpressing MYB221-SRDX and MYB156 showed a decrease in fiber cell wall lignification, and a reduced growth. MYB221 have targets encoding for metabolic enzymes but also for another R2R3-MYB TF. MYB221 recognizes its target genes, most probably through SMRE (Secondary wall MYB-Responsive Element) conserved motif. In conclusion, the combination of ChIP-SEQ and genetic engineering approaches shows that MYB090 seems to be a transcriptional repressor of lignification, especially in parenchyma rays. MYB156 and MYB221 are also negative regulators of secondary cell wall lignification, in fibers and parenchyma rays. This work opens new avenues on the building of transcriptional regulatory networks involved in secondary cell wall formation
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Masson, Florent Le. "Caractérisation des facteurs HSF1 et HSF2 en tant que facteur maternel et régulateur de la réponse au stress." Toulouse 3, 2010. http://www.theses.fr/2010TOU30277.
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Au cours de ma thèse, je me suis intéressé aux facteurs de choc thermique HSFs (Heat Shock Factors) et aux fonctions qu'ils exercent au cours du développement. Mon projet de thèse comportait deux parties principales, la première concernant l'identification des gènes cibles du facteur maternel HSF1, et la seconde concernant les fonctions d'HSF1 et HSF2 au cours du développement précoce. Dans un premier temps, nous avons donc cherché à identifier les gènes cibles du facteur HSF1 par une analyse transcriptomique afin de mieux caractériser sa fonction maternelle dans l'ovocyte de souris. Ainsi, parmi les gènes régulés par HSF1, nous avons observé un enrichissement en gènes impliqués dans la cohésion des chromosomes homologues et des chromatides sœurs et nous avons mis en évidence la présence d'HSF1 sur le promoteur de 4 de ces gènes : Stag2, Stag3, Syce1 et Msh4. Ensuite, nous avons mis en évidence que la réduction de ces gènes dans les ovocytes Hsf1-/- entraine des défauts de progression à travers la prophase I aboutissant à une ségrégation précoce des chromosomes homologues lors de la métaphase I. L'ensemble de ces données montrent qu'HSF1 participe à la coordination de la dynamique des chromosomes au cours de la méiose chez la femelle. La deuxième partie de mon projet de thèse concernait les fonctions exercées par HSF1 et HSF2 au cours du développement précoce. En combinant l'utilisation de lignées transgéniques rapportrices (Hsp70. 1 Luciférase) et de lignées mutantes pour Hsf1 ou Hsf2 (Hsf1-/-, Hsf2-/-), nous avons montré qu’HSF1 et HSF2 jouent un rôle dans l’activation zygotique du gène Hsp70. 1 et qu’HSF2 intervient dans la réponse au choc thermique au stade blastocysteDuring my PhD, I studied heat shock factors HSFs and their functions during development. My thesis project included two main parts. The first one was aimed to identify HSF1 dependent target genes, and the second part investigated the functions of HSF1 and HSF2 during early development. First, we sought to identify HSF1 target genes by a transcriptome analysis to further characterize its maternal function in mouse oocyte. Among the genes regulated by HSF1, we observed an enrichment of genes involved in the cohesion of homologous chromosomes and sister chromatids and we observed the presence of HSF1 on the promoter of 4 of these genes: Stag2, Stag3, Syce1 and Msh4. Then, we demonstrated that the lower expression of these genes in Hsf1-/- oocytes led to defects in prophase I progression and early segregation of homologous chromosomes at metaphase I. Taken together, these data show that HSF1 helps to coordinate the dynamics of chromosomes during female meiosis in mammals. The second part of my project was about the functions performed by HSF1 and HSF2 during early development. Using several mouse transgenic and knockout lines, we showed that HSF1 and HSF2 play a role in the activation of zygotic Hsp70. 1 and that HSF2 takes part to the heat shock response at the blastocyst stage
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Cauchy, Pierre. "Rôle et contexte transcriptionnel du facteur de transcription Ets1 au cours transition CD4- CD8- à CD4+ CD8+ de la tymopoïèse αβ." Thesis, Aix-Marseille 2, 2010. http://www.theses.fr/2010AIX22135.
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ETS1 est un facteur de transcription (FT) spécifique transposé dans les leucémies aigües. Le rôle essentiel d'ETS1 a été décrit au cours de l'hématopoïèse, plus particulièrement dans la différenciation lymphocytaire T. Son expression temporelle coordonnée participe au contrôle des transitions du stade double négatif (DN) CD4-/CD8- au stade double positif (DP) CD4+/CD8+jusqu'au stade simple positif (SP) CD4+ ou CD8+. Au cours de l'ontogenèse T, ETS1 transactive notamment l'expression des chaînes β et α du récepteur des cellules T (TCR). Nous avons criblé à grande échelle les cibles d'ETS1 aux stades DN et DP en ChIP-Seq, ainsi que desmarques histone et de l'ARN polymérase II (Pol II). Afin de faciliter nos analyses bioinformatiques, nous avons développé deux logiciels, CoCAS et AmaMineReg, qui permettent d'identifier plus facilement les cibles à partir de données brutes et de discriminer les vrais des faux positifs. Nous avons trouvé 5900 cibles en DN et 3400 en DP, principalement intergéniques dont 2000 sont communes, non caractérisées et correspondent aux gènes induits par la réponse immédiate à la signalisation TCR. Parmi les cibles différentiellement exprimées entre les deux stades, ETS1 active les gènes thymus-spécifiques et réprime les gènes hématopoïétiques non T spécifiques,en fonction de la co-occurrence avec le motif RUNX1. Nous avons également caractérisé très clairement le site de fixation en conditions natives, qui se révèle être CTTCCT.De plus, ETS1 co-localise avec des marques chromatines permissives aux régions inter- et intragéniques,caractérisées par un contenu GC, densité de motifs de fixation de FT (SFFT) et conservation inter-espèces accrusETS1 is a specific transcription factor (TF) transposed in acute leukemias. key role of ETS1 wasdescribed during hematopoiesis, especially in T lymphocyte differentiation. Its temporal expression participates in the coordinated control of phase transitions from the CD4-/CD8-double negative (DN) stage to CD4+/CD8+ double positive (DP) up to CD4 or CD8 single positivestage (SP). During ontogenesis T ETS1 notably transactivates the expression of the alpha and beta chains of the T-Cell receptor (TCR). We performed genome-wide screening of ETS1 at both DN and DP stages via ChIP-Seq, as well as histone hallmarks and RNA polymerase II (PolII). To facilitate computational analysis we developed two new software suites, and COCASAmaMineReg, which allow easier identification of targets from raw data and to discriminate between true and false positives. We found 5900 targets in 3400 in DN and DP, mostly intergenic, out of which 2000 are common, and correspond to uncharacterized genes induced bythe immediate response to TCR signaling. Among targets differentially expressed between thetwo stages, Ets1 activates thymus-specific genes and represses non T-specific haematopoietic genes depending on the co-occurrence with the RUNX1 motif. We also very clearly characterized the binding site in native conditions, which proved to be CTTCCT. Furthermore, Ets1 colocalizes with permissive chromatin marks in inter-and intra-genic regions, characterized byincreased GC content, TF binding motifs (TFBS) density as well as inter-species conservation
Books on the topic "Facteur de transcription CHOP"
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Littlewood, Trevor D. Helix-loop-helix transcription factors. 3rd ed. Oxford: Oxford University Press, 1998.
Find full textBook chapters on the topic "Facteur de transcription CHOP"
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Jaini, Suma, Anna Lyubetskaya, Antonio Gomes, Matthew Peterson, Sang Tae Park, Sahadevan Raman, Gary Schoolnik, and James Galagan. "Transcription Factor Binding Site Mapping Using ChIP-Seq." In Molecular Genetics of Mycobacteria, 161–81. Washington, DC, USA: ASM Press, 2015. http://dx.doi.org/10.1128/9781555818845.ch8.
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Ron, D. "TLS-CHOP and the Role of RNA-Binding Proteins in Oncogenic Transformation." In Chromosomal Translocations and Oncogenic Transcription Factors, 131–42. Berlin, Heidelberg: Springer Berlin Heidelberg, 1997. http://dx.doi.org/10.1007/978-3-642-60479-9_8.
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Barski, Artem, Steven Pregizer, and Baruch Frenkel. "Identification of Transcription Factor Target Genes by ChIP Display." In Osteoporosis, 177–90. Totowa, NJ: Humana Press, 2008. http://dx.doi.org/10.1007/978-1-59745-104-8_14.
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Fomin, Vitalay, and Carol Prives. "Discovering Transcription Factor Noncoding RNA Targets Using ChIP-Seq Analysis." In Methods in Molecular Biology, 305–12. New York, NY: Springer US, 2020. http://dx.doi.org/10.1007/978-1-0716-0247-8_26.
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Ghavi-Helm, Yad, and Eileen E. M. Furlong. "Analyzing Transcription Factor Occupancy During Embryo Development Using ChIP-seq." In Methods in Molecular Biology, 229–45. Totowa, NJ: Humana Press, 2011. http://dx.doi.org/10.1007/978-1-61779-292-2_14.
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Pillai, Smitha, and Srikumar P. Chellappan. "ChIP on Chip Assays: Genome-Wide Analysis of Transcription Factor Binding and Histone Modifications." In Methods in Molecular Biology, 341–66. Totowa, NJ: Humana Press, 2009. http://dx.doi.org/10.1007/978-1-59745-190-1_23.
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Pillai, Smitha, and Srikumar P. Chellappan. "ChIP on Chip and ChIP-Seq Assays: Genome-Wide Analysis of Transcription Factor Binding and Histone Modifications." In Methods in Molecular Biology, 447–72. New York, NY: Springer New York, 2015. http://dx.doi.org/10.1007/978-1-4939-2474-5_26.
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Kallio, Aleksi, and Laura L. Elo. "Optimizing Detection of Transcription Factor-Binding Sites in ChIP-seq Experiments." In Methods in Molecular Biology, 181–91. Totowa, NJ: Humana Press, 2013. http://dx.doi.org/10.1007/978-1-62703-514-9_11.
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Schödel, Johannes, and David R. Mole. "Mapping the HIF Transcription Factor in Cancer by ChIP-Seq Technology." In Next Generation Sequencing in Cancer Research, 91–117. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4614-7645-0_5.
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Li, Juntao, Lei Zhu, Majid Eshaghi, Jianhua Liu, and Radha Krishna Murthy Karuturi. "Deciphering Transcription Factor Binding Patterns from Genome-Wide High Density ChIP-chip Tiling Array Data." In Bioinformatics Research and Applications, 230–40. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-642-13078-6_25.
Full textConference papers on the topic "Facteur de transcription CHOP"
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Chen, Ting, and Feng Li. "Identifying Combinatorial Transcription Factor Interactions with Microarray Data and ChIP-Chip Data." In 2008 2nd International Conference on Bioinformatics and Biomedical Engineering. IEEE, 2008. http://dx.doi.org/10.1109/icbbe.2008.61.
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Munoz, Matthew, and Alexander Zambon. "InSilico-ChIP: A Coregulation and Evolutionary Conservation Based Transcription Factor and Target Gene Predictor." In 2012 IEEE Second International Conference on Healthcare Informatics, Imaging and Systems Biology (HISB). IEEE, 2012. http://dx.doi.org/10.1109/hisb.2012.47.
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Fu, Junjiang. "Abstract 2902: Global bioinformatic analysis for transcription factor genomic binding sites from ChIP-sequencing." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-2902.
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Orlov, Yuriy L., Neil D. Clarke, Huck H. Ng, Mikael E. Huss, Roy Joseph, Han Xu, Vinsensius B. Vega, et al. "Genome-wide statistical analysis of multiple transcription factor binding sites obtained by chip-seq technologies." In the 1st ACM workshop. New York, New York, USA: ACM Press, 2009. http://dx.doi.org/10.1145/1531780.1531784.
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Oh, You-Take. "Abstract 1066: ERK/RSK and JNK signaling cooperatively mediate oncogenic Ras-induced death receptor 5 expression through enhancing CHOP, Elk1 and c-Jun-dependent transcription." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-1066.
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KUZNETSOV, VLADIMIR A., YURIY L. ORLOV, CHIA LIN WEI, and YIJUN RUAN. "COMPUTATIONAL ANALYSIS AND MODELING OF GENOME-SCALE AVIDITY DISTRIBUTION OF TRANSCRIPTION FACTOR BINDING SITES IN CHIP-PET EXPERIMENTS." In Proceedings of the 18th International Conference. PUBLISHED BY IMPERIAL COLLEGE PRESS AND DISTRIBUTED BY WORLD SCIENTIFIC PUBLISHING CO., 2007. http://dx.doi.org/10.1142/9781860949852_0008.
Full textReports on the topic "Facteur de transcription CHOP"
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Eshed-Williams, Leor, and Daniel Zilberman. Genetic and cellular networks regulating cell fate at the shoot apical meristem. United States Department of Agriculture, January 2014. http://dx.doi.org/10.32747/2014.7699862.bard.
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The shoot apical meristem establishes plant architecture by continuously producing new lateral organs such as leaves, axillary meristems and flowers throughout the plant life cycle. This unique capacity is achieved by a group of self-renewing pluripotent stem cells that give rise to founder cells, which can differentiate into multiple cell and tissue types in response to environmental and developmental cues. Cell fate specification at the shoot apical meristem is programmed primarily by transcription factors acting in a complex gene regulatory network. In this project we proposed to provide significant understanding of meristem maintenance and cell fate specification by studying four transcription factors acting at the meristem. Our original aim was to identify the direct target genes of WUS, STM, KNAT6 and CNA transcription factor in a genome wide scale and the manner by which they regulate their targets. Our goal was to integrate this data into a regulatory model of cell fate specification in the SAM and to identify key genes within the model for further study. We have generated transgenic plants carrying the four TF with two different tags and preformed chromatin Immunoprecipitation (ChIP) assay to identify the TF direct target genes. Due to unforeseen obstacles we have been delayed in achieving this aim but hope to accomplish it soon. Using the GR inducible system, genetic approach and transcriptome analysis [mRNA-seq] we provided a new look at meristem activity and its regulation of morphogenesis and phyllotaxy and propose a coherent framework for the role of many factors acting in meristem development and maintenance. We provided evidence for 3 different mechanisms for the regulation of WUS expression, DNA methylation, a second receptor pathway - the ERECTA receptor and the CNA TF that negatively regulates WUS expression in its own domain, the Organizing Center. We found that once the WUS expression level surpasses a certain threshold it alters cell identity at the periphery of the inflorescence meristem from floral meristem to carpel fate [FM]. When WUS expression highly elevated in the FM, the meristem turn into indeterminate. We showed that WUS activate cytokinine, inhibit auxin response and represses the genes required for root identity fate and that gradual increase in WUCHEL activity leads to gradual meristem enlargement that affect phyllotaxis. We also propose a model in which the direction of WUS domain expansion laterally or upward affects meristem structure differently. We preformed mRNA-seq on meristems with different size and structure followed by k-means clustering and identified groups of genes that are expressed in specific domains at the meristem. We will integrate this data with the ChIP-seq of the 4 TF to add another layer to the genetic network regulating meristem activity.
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Barg, Rivka, Erich Grotewold, and Yechiam Salts. Regulation of Tomato Fruit Development by Interacting MYB Proteins. United States Department of Agriculture, January 2012. http://dx.doi.org/10.32747/2012.7592647.bard.
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Background to the topic: Early tomato fruit development is executed via extensive cell divisions followed by cell expansion concomitantly with endoreduplication. The signals involved in activating the different modes of growth during fruit development are still inadequately understood. Addressing this developmental process, we identified SlFSM1 as a gene expressed specifically during the cell-division dependent stages of fruit development. SlFSM1 is the founder of a class of small plant specific proteins containing a divergent SANT/MYB domain (Barg et al 2005). Before initiating this project, we found that low ectopic over-expression (OEX) of SlFSM1 leads to a significant decrease in the final size of the cells in mature leaves and fruits, and the outer pericarp is substantially narrower, suggesting a role in determining cell size and shape. We also found the interacting partners of the Arabidopsis homologs of FSM1 (two, belonging to the same family), and cloned their tomato single homolog, which we named SlFSB1 (Fruit SANT/MYB–Binding1). SlFSB1 is a novel plant specific single MYB-like protein, which function was unknown. The present project aimed at elucidating the function and mode of action of these two single MYB proteins in regulating tomato fruit development. The specific objectives were: 1. Functional analysis of SlFSM1 and its interacting protein SlFSB1 in relation to fruit development. 2. Identification of the SlFSM1 and/or SlFSB1 cellular targets. The plan of work included: 1) Detailed phenotypic, histological and cellular analyses of plants ectopically expressing FSM1, and plants either ectopically over-expressing or silenced for FSB1. 2) Extensive SELEX analysis, which did not reveal any specific DNA target of SlFSM1 binding, hence the originally offered ChIP analysis was omitted. 3) Genome-wide transcriptional impact of gain- and loss- of SlFSM1 and SlFSB1 function by Affymetrix microarray analyses. This part is still in progress and therefore results are not reported, 4) Search for additional candidate partners of SlFSB1 revealed SlMYBI to be an alternative partner of FSB1, and 5) Study of the physical basis of the interaction between SlFSM1 and SlFSB1 and between FSB1 and MYBI. Major conclusions, solutions, achievements: We established that FSM1 negatively affects cell expansion, particularly of those cells with the highest potential to expand, such as the ones residing inner to the vascular bundles in the fruit pericarp. On the other hand, FSB1 which is expressed throughout fruit development acts as a positive regulator of cell expansion. It was also established that besides interacting with FSM1, FSB1 interacts also with the transcription factor MYBI, and that the formation of the FSB1-MYBI complex is competed by FSM1, which recognizes in FSB1 the same region as MYBI does. Based on these findings a model was developed explaining the role of this novel network of the three different MYB containing proteins FSM1/FSB1/MYBI in the control of tomato cell expansion, particularly during fruit development. In short, during early stages of fruit development (Phase II), the formation of the FSM1-FSB1 complex serves to restrict the expansion of the cells with the greatest expansion potential, those non-dividing cells residing in the inner mesocarp layers of the pericarp. Alternatively, during growth phase III, after transcription of FSM1 sharply declines, FSB1, possibly through complexing with the transcription factor MYBI serves as a positive regulator of the differential cell expansion which drives fruit enlargement during this phase. Additionally, a novel mechanism was revealed by which competing MYB-MYB interactions could participate in the control of gene expression. Implications, both scientific and agricultural: The demonstrated role of the FSM1/FSB1/MYBI complex in controlling differential cell growth in the developing tomato fruit highlights potential exploitations of these genes for improving fruit quality characteristics. Modulation of expression of these genes or their paralogs in other organs could serve to modify leaf and canopy architecture in various crops.
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Casey, Therese, Sameer J. Mabjeesh, Avi Shamay, and Karen Plaut. Photoperiod effects on milk production in goats: Are they mediated by the molecular clock in the mammary gland? United States Department of Agriculture, January 2014. http://dx.doi.org/10.32747/2014.7598164.bard.
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US scientists, Dr. Theresa Casey and Dr. Karen Plaut, collaborated with Israeli scientists, Dr. SameerMabjeesh and Dr. AviShamay to conduct studies proposed in the BARD Project No. US-4715-14 Photoperiod effects on milk production in goats: Are they mediated by the molecular clock in the mammary gland over the last 3 years. CLOCK and BMAL1 are core components of the circadian clock and as heterodimers function as a transcription factor to drive circadian-rhythms of gene expression. Studies of CLOCK-mutant mice found impaired mammary development in late pregnancy was related to poor lactation performance post-partum. To gain a better understanding of role of clock in regulation of mammary development studies were conducted with the mammary epithelial cell line HC11. Decreasing CLOCK protein levels using shRNA resulted in increased mammary epithelial cell growth rate and impaired differentiation, with lower expression of differentiation markers including ad herens junction protein and fatty acid synthesis genes. When BMAL1 was knocked out using CRISPR-CAS mammary epithelial cells had greater growth rate, but reached stationary phase at a lower density, with FACS indicating cells were growing and dying at a faster rate. Beta-casein milk protein levels were significantly decreased in BMAL1 knockout cells. ChIP-seq analysis was conducted to identify BMAL1 target genes in mammary epithelial cells. Studies conducted in goats found that photoperiod duration and physiological state affected the dynamics of the mammary clock. Effects were likely independent of the photoperiod effects on prolactin levels. Interestingly, circadian rhythms of core body temperature, which functions as a key synchronizing cue sent out by the central clock in the hypothalamus, were profoundly affected by photoperiod and physiological state. Data support that the clock in the mammary gland regulates genes important to development of the gland and milk synthesis. We also found the clock in the mammary is responsive to changes in physiological state and photoperiod, and thus may serve as a mechanism to establish milk production levels in response to environmental cues.