20 results on '"Mietton, Flore"'
Search Results
2. Genetic analyses of a large cohort of infertile patients with globozoospermia, DPY19L2 still the main actor, GGN confirmed as a guest player
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Celse, Tristan, Cazin, Caroline, Mietton, Flore, Martinez, Guillaume, Martinez, Delphine, Thierry-Mieg, Nicolas, Septier, Amandine, Guillemain, Catherine, Beurois, Julie, Clergeau, Antoine, Mustapha, Selima Fourati Ben, Kharouf, Mahmoud, Zoghmar, Abdelali, Chargui, Ahmed, Papaxanthos, Aline, Dorphin, Béatrice, Foliguet, Bernard, Triki, Chema, Sifer, Christophe, Lauton, Dominique, Tachdjian, Gérard, Schuler, Gilles, Lejeune, Hervé, Puechberty, Jacques, Bessonnat, Julien, Pasquier, Laurent, Mery, Lionel, Poulain, Marine, Chaabouni, Myriam, Sermondade, Nathalie, Cabry, Rosalie, Benbouhadja, Sebti, Veau, Ségolène, Frapsauce, Cynthia, Mitchell, Valérie, Achard, Vincent, Satre, Veronique, Hennebicq, Sylviane, Zouari, Raoudha, Arnoult, Christophe, Kherraf, Zine-Eddine, Coutton, Charles, and Ray, Pierre F.
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- 2021
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3. Requirement for the histone deacetylase Hdac3 for the inflammatory gene expression program in macrophages
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Chen, Xuefen, Barozzi, Iros, Termanini, Alberto, Prosperini, Elena, Recchiuti, Antonio, Dalli, Jesmond, Mietton, Flore, Matteoli, Gianluca, Hiebert, Scott, and Natoli, Gioacchino
- Published
- 2012
4. Genetic analyses of a large cohort of infertile patients with globozoospermia, DPY19L2 still the main actor, GGN confirmed as a guest player
- Author
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Celse, Tristan, primary, Cazin, Caroline, additional, Mietton, Flore, additional, Martinez, Guillaume, additional, Martinez, Delphine, additional, Thierry-Mieg, Nicolas, additional, Septier, Amandine, additional, Guillemain, Catherine, additional, Beurois, Julie, additional, Clergeau, Antoine, additional, Mustapha, Selima Fourati Ben, additional, Kharouf, Mahmoud, additional, Zoghmar, Abdelali, additional, Chargui, Ahmed, additional, Papaxanthos, Aline, additional, Dorphin, Béatrice, additional, Foliguet, Bernard, additional, Triki, Chema, additional, Sifer, Christophe, additional, Lauton, Dominique, additional, Tachdjian, Gérard, additional, Schuler, Gilles, additional, Lejeune, Hervé, additional, Puechberty, Jacques, additional, Bessonnat, Julien, additional, Pasquier, Laurent, additional, Mery, Lionel, additional, Poulain, Marine, additional, Chaabouni, Myriam, additional, Sermondade, Nathalie, additional, Cabry, Rosalie, additional, Benbouhadja, Sebti, additional, Veau, Ségolène, additional, Frapsauce, Cynthia, additional, Mitchell, Valérie, additional, Achard, Vincent, additional, Satre, Veronique, additional, Hennebicq, Sylviane, additional, Zouari, Raoudha, additional, Arnoult, Christophe, additional, Kherraf, Zine-Eddine, additional, Coutton, Charles, additional, and Ray, Pierre F., additional
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- 2020
- Full Text
- View/download PDF
5. Identification and Characterization of Enhancers Controlling the Inflammatory Gene Expression Program in Macrophages
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Ghisletti, Serena, Barozzi, Iros, Mietton, Flore, Polletti, Sara, De Santa, Francesca, Venturini, Elisa, Gregory, Lorna, Lonie, Lorne, Chew, Adeline, Wei, Chia-Lin, Ragoussis, Jiannis, and Natoli, Gioacchino
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- 2010
- Full Text
- View/download PDF
6. A new hope to fight invasive fungal infection
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Petosa, Carlo, Govin, Jérôme, Mietton, Flore, Institut de biologie structurale [1992-2019] (IBS - UMR 5075 [1992-2019]), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Etude de la dynamique des protéomes [?-2019] (EDyP [?-2019]), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Etude de la dynamique des protéomes (EDyP )
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[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,[SDV]Life Sciences [q-bio] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2018
7. Champignons pathogènes
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Petosa, Carlo, Govin, Jérôme, Mietton, Flore, Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Etude de la dynamique des protéomes (EDyP ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Thomas, Frank
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[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,[SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2018
8. Bdf1 Bromodomains Are Essential for Meiosis and the Expression of Meiotic-Specific Genes
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García-Oliver, Encar, Ramus, Claire, Perot, Jonathan, Arlotto, Marie, Champleboux, Morgane, Mietton, Flore, Battail, Christophe, Boland, Anne, Deleuze, Jean-François, Ferro, Myriam, Couté, Yohann, Govin, Jérôme, Développement de la protéomique comme outil d'investigation fonctionelle et d'annotation des génomes, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biosciences et de Biotechnologies de Grenoble (ex-IRTSV) (BIG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Biologie moléculaire et cellulaire de la différenciation, Université Joseph Fourier - Grenoble 1 (UJF)-Institut Albert Bonniot-Institut National de la Santé et de la Recherche Médicale (INSERM), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Département Santé (DSANTE), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Etude de la dynamique des protéomes (EDyP ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Grenoble Alpes (UGA), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Université Grenoble Alpes (UGA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Etude de la dynamique des protéomes (EDyP), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
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Saccharomyces cerevisiae Proteins ,lcsh:QH426-470 ,[SDV]Life Sciences [q-bio] ,DNA transcription ,Gene Expression ,Yeast and Fungal Models ,Saccharomyces cerevisiae ,Research and Analysis Methods ,Biochemistry ,Histones ,Saccharomyces ,Model Organisms ,DNA-binding proteins ,Genetics ,Gene Regulation ,Cell Cycle and Cell Division ,ComputingMilieux_MISCELLANEOUS ,Adenosine Triphosphatases ,Binding Sites ,Chromosome Biology ,Organisms ,Fungi ,Biology and Life Sciences ,Proteins ,Cell Biology ,Chromatin ,Yeast ,Mutant Strains ,Meiosis ,lcsh:Genetics ,Experimental Organism Systems ,Cell Processes ,Mutation ,Epigenetics ,Research Article ,Protein Binding ,Transcription Factors - Abstract
Bromodomain and Extra-terminal motif (BET) proteins play a central role in transcription regulation and chromatin signalling pathways. They are present in unicellular eukaryotes and in this study, the role of the BET protein Bdf1 has been explored in Saccharomyces cerevisiae. Mutation of Bdf1 bromodomains revealed defects on both the formation of spores and the meiotic progression, blocking cells at the exit from prophase, before the first meiotic division. This phenotype is associated with a massive deregulation of the transcription of meiotic genes and Bdf1 bromodomains are required for appropriate expression of the key meiotic transcription factor NDT80 and almost all the Ndt80-inducible genes, including APC complex components. Bdf1 notably accumulates on the promoter of Ndt80 and its recruitment is dependent on Bdf1 bromodomains. In addition, the ectopic expression of NDT80 during meiosis partially bypasses this dependency. Finally, purification of Bdf1 partners identified two independent complexes with Bdf2 or the SWR complex, neither of which was required to complete sporulation. Taken together, our results unveil a new role for Bdf1 –working independently from its predominant protein partners Bdf2 and the SWR1 complex–as a regulator of meiosis-specific genes., Author Summary Chromatin modifying proteins play a central role in transcription regulation and chromatin signalling. In this study we investigated the functional role of the bromodomains of the chromatin protein Bdf1 during yeast gametogenesis. Our results show that the bromodomains of Bdf1 are essential for meiotic progression and the formation of mature spores. Bdf1 bromodomains are required for the expression of key meiotic genes and the master regulator NDT80. Forced expression of NDT80 can partially rescue the formation of spores when Bdf1 bromodomains are mutated. The results presented here indicate that Bdf1 forms two exclusive complexes, with Bdf2 or with the SWR complex. However, none of these complexes are required for sporulation progression. To conclude, our findings suggest that Bdf1 is a new regulator of the meiotic transcription program and of the expression of the master regulator NDT80.
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- 2017
9. Selective BET bromodomain inhibition as an antifungal therapeutic strategy
- Author
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Mietton, Flore, primary, Ferri, Elena, additional, Champleboux, Morgane, additional, Zala, Ninon, additional, Maubon, Danièle, additional, Zhou, Yingsheng, additional, Harbut, Mike, additional, Spittler, Didier, additional, Garnaud, Cécile, additional, Courçon, Marie, additional, Chauvel, Murielle, additional, d’Enfert, Christophe, additional, Kashemirov, Boris A., additional, Hull, Mitchell, additional, Cornet, Muriel, additional, McKenna, Charles E., additional, Govin, Jérôme, additional, and Petosa, Carlo, additional
- Published
- 2017
- Full Text
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10. Localisation et fonction du variant d'histone macroH2A
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Mietton, Flore, Biologie moléculaire et cellulaire de la différenciation, Université Joseph Fourier - Grenoble 1 (UJF)-Institut Albert Bonniot-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph-Fourier - Grenoble I, Annie Molla, and Mietton, Flore
- Subjects
macroH2Achromosome X inactif ,réparation de l'ADNPARP-1ARN interférence ,«ChIP-on-CHIP» ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,variant d'histone ,[SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,répression transcriptionnelle ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM] - Abstract
MacroH2A (mH2A) is an unusual histone variant which consists of a histone-like domain and a non-histone region (NHR). Immunofluorescence data suggested that macroH2A is accumulated at the inactive X chromosome. In this work we have used chromatin immunoprecipitation (ChIP) analysis, combined with human and mouse genome-wide array hybridization (ChIP on CHIP), to investigate the association of mH2A with the inactive X chromosome. The mH2A enrichment is moderate, suggesting a non-essential mH2A participation to the X inactivationWe describe a novel function of mH2A, namely its involvement in DNA repair. In vivo mH2A1 nucleosomes are found associated with PARP-1 and in vitro experiments demonstrate that the NHR domain of mH2A1 is essential for this interaction. The siRNA suppression of the expression of mH2A1 affects cell survival after oxidative DNA damage and inhibition of PARP-1 enzymatic activity abolishes this effect. The absence of mH2A1 results in overactivation of PARP-1 and compromises severely DNA repair after oxidative damage. Rescue experiments with silent resistant mutants of mH2A1 evidence that the NHR, but not the H2A-like domain of mH2A1, is required for the efficient repair of DNA. These data show that the involvement of mH2A1 in the repair of DNA is realized through a PARP-1 repair pathway., La structure de la chromatine et sa compaction sont modulées par la substitution des histones conventionnelles par des variants d'histones. MacroH2A est l'un de ces variants et se singularise par sa grande taille. De nombreuses données suggèrent que macroH2A pourrait participer à l'inactivation de la transcription.Par immunofluorescence, cette protéine est retrouvée accumulée sur le territoire du chromosome X inactif (Xi) chez les mammifères femelles. Néanmoins, cette association préférentielle pourrait simplement refléter la forte concentration en nucléosomes de cette région. Pour aborder le rôle de macroH2A dans le phénomène de l'inactivation du chromosome X, notre principale approche a consisté en des expériences de «ChIP-on-CHIP» sur de la chromatine native. Nos résultats montrent un enrichissement global et modeste de macroH2A sur le chromosome X femelle, excepté sur la plupart des gènes échappant à l'inactivation. Nous avons souhaité nous intéresser également au rôle potentiel de macroH2A dans le mécanisme de réparation de l'ADN. En effet, il a été montré que le domaine macro est capable de lier l'ADP-ribose, un nucléotide déterminant dans de nombreux processus biologiques tels que la transcription ou la réparation. Plusieurs expériences nous ont permis de démontrer que les nucléosomes macroH2A sont associés in vivo à l'enzyme PARP-1, protéine clef de la réparation des cassures simple brin de l'ADN. La PARP-1 associée au nucléosome variant est inactive, et le traitement par H2O2 va induire son relâchement et son activation. L'absence de macroH2A conduit à une sur-activation de PARP-1, ce qui compromet sévèrement la réparation de l'ADN endommagé.
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- 2007
11. Flexible Synthesis and Evaluation of Diverse Anti-Apicomplexa Cyclic Peptides
- Author
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Traoré, Mariam, primary, Mietton, Flore, additional, Maubon, Danièle, additional, Peuchmaur, Marine, additional, Francisco Hilário, Flaviane, additional, Pereira de Freitas, Rossimiriam, additional, Bougdour, Alexandre, additional, Curt, Aurélie, additional, Maynadier, Marjorie, additional, Vial, Henri, additional, Pelloux, Hervé, additional, Hakimi, Mohamed-Ali, additional, and Wong, Yung-Sing, additional
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- 2013
- Full Text
- View/download PDF
12. Champignons pathogènes: Un nouvel espoir de traitement des infections généralisées.
- Author
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Petosa, Carlo, Govin, Jérôme, and Mietton, Flore
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- 2018
- Full Text
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13. Rapamycin-sensitive signals control TCR/CD28-drivenIfng,Il4andFoxp3transcription and promoter region methylation
- Author
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Tomasoni, Romana, primary, Basso, Veronica, additional, Pilipow, Karolina, additional, Sitia, Giovanni, additional, Saccani, Simona, additional, Agresti, Alessandra, additional, Mietton, Flore, additional, Natoli, Gioacchino, additional, Colombetti, Sara, additional, and Mondino, Anna, additional
- Published
- 2011
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14. A Large Fraction of Extragenic RNA Pol II Transcription Sites Overlap Enhancers
- Author
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De Santa, Francesca, primary, Barozzi, Iros, additional, Mietton, Flore, additional, Ghisletti, Serena, additional, Polletti, Sara, additional, Tusi, Betsabeh Khoramian, additional, Muller, Heiko, additional, Ragoussis, Jiannis, additional, Wei, Chia-Lin, additional, and Natoli, Gioacchino, additional
- Published
- 2010
- Full Text
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15. Weak but Uniform Enrichment of the Histone Variant macroH2A1 along the Inactive X Chromosome
- Author
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Mietton, Flore, primary, Sengupta, Aditya K., additional, Molla, Annie, additional, Picchi, Gisele, additional, Barral, Sophie, additional, Heliot, Laurent, additional, Grange, Thierry, additional, Wutz, Anton, additional, and Dimitrov, Stefan, additional
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- 2009
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16. The histone variant mH2A1.1 interferes with transcription by down-regulating PARP-1 enzymatic activity
- Author
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Ouararhni, Khalid, primary, Hadj-Slimane, Réda, additional, Ait-Si-Ali, Slimane, additional, Robin, Philippe, additional, Mietton, Flore, additional, Harel-Bellan, Annick, additional, Dimitrov, Stefan, additional, and Hamiche, Ali, additional
- Published
- 2006
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17. Nucleolin is a histone chaperone with FACT-like activity and assists remodeling of nucleosomes
- Author
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Angelov, Dimitar, primary, Bondarenko, Vladimir A, additional, Almagro, Sébastien, additional, Menoni, Hervé, additional, Mongélard, Fabien, additional, Hans, Fabienne, additional, Mietton, Flore, additional, Studitsky, Vasily M, additional, Hamiche, Ali, additional, Dimitrov, Stefan, additional, and Bouvet, Philippe, additional
- Published
- 2006
- Full Text
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18. Mechanism of Polymerase II Transcription Repression by the Histone Variant macroH2A
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Doyen, Cécile-Marie, primary, An, Woojin, additional, Angelov, Dimitar, additional, Bondarenko, Vladimir, additional, Mietton, Flore, additional, Studitsky, Vassily M., additional, Hamiche, Ali, additional, Roeder, Robert G., additional, Bouvet, Philippe, additional, and Dimitrov, Stefan, additional
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- 2006
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19. Seasonal environmental changes regulate the expression of the histone variant macroH2A in an eurythermal fish
- Author
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Pinto, Rodrigo, primary, Ivaldi, Corinne, additional, Reyes, Mauricio, additional, Doyen, Cécile, additional, Mietton, Flore, additional, Mongelard, Fabien, additional, Alvarez, Marco, additional, Molina, Alfredo, additional, Dimitrov, Stefan, additional, Krauskopf, Manuel, additional, Vera, Maria Ines, additional, and Bouvet, Philippe, additional
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- 2005
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20. Rapamycin-sensitive signals control TCR/CD28-driven Ifng, Il4 and Foxp3 transcription and promoter region methylation.
- Author
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Tomasoni, Romana, Basso, Veronica, Pilipow, Karolina, Sitia, Giovanni, Saccani, Simona, Agresti, Alessandra, Mietton, Flore, Natoli, Gioacchino, Colombetti, Sara, and Mondino, Anna
- Abstract
The mammalian target of rapamycin (mTOR) controls T-cell differentiation in response to polarizing cytokines. We previously found that mTOR blockade by rapamycin (RAPA) delays the G1-S cell cycle transition and lymphocyte proliferation. Here, we report that both mTOR complex 1 and mTOR complex 2 are readily activated following TCR/CD28 engagement and are critical for early expression of Ifng, Il4 and Foxp3, and for effector T cell differentiation in the absence of polarizing cytokines. While inhibition of mTOR complex 1 and cell division were evident at low doses of RAPA, inhibition of mTOR complex 2, Ifng, Il4 and Foxp3 expression, and T-cell polarization required higher doses and more prolonged treatments. We found that while T-bet and GATA3 were readily induced following TCR/CD28 engagement, administration of RAPA delayed their expression, and interfered with the loss of DNA methylation within Ifng and Il4 promoter regions. In contrast, RAPA prevented activation-dependent DNA methylation of the Foxp3 promoter favoring Foxp3 expression. As a result, RAPA-cultured cells lacked immediate effector functions and instead were enriched for IL-2 cells. We propose that mTOR-signaling, by timing the expression of critical transcription factors and DNA methylation of proximal promoter regions, regulates transcriptional competence at immunologically relevant sites and hence lymphocyte differentiation. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
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