16 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
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- 2012
4. 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
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5. 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 )
- Subjects
[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
6. Champignons pathogènes
- Author
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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
7. 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
8. Seasonal environmental changes regulate the expression of the histone variant macroH2A in an eurythermal fish
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Pinto, Rodrigo, Ivaldi, Corinne, Reyes, Mauricio, Doyen, Cécile, Mietton, Flore, Mongelard, Fabien, Alvarez, Marco, Molina, Alfredo, Dimitrov, Stefan, Krauskopf, Manuel, Vera, Maria Ines, and Bouvet, Philippe
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- 2005
- Full Text
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9. Flexible Synthesis and Evaluation of Diverse Anti-Apicomplexa Cyclic Peptides.
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Traoré, Mariam, Mietton, Flore, Maubon, Danièle, Peuchmaur, Marine, Francisco Hilário, Flaviane, Pereira de Freitas, Rossimiriam, Bougdour, Alexandre, Curt, Aurélie, Maynadier, Marjorie, Vial, Henri, Pelloux, Hervé, Hakimi, Mohamed-Ali, and Yung-Sing Wong
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PEPTIDE synthesis , *SCAFFOLD proteins , *RADICALS (Chemistry) , *TOXOPLASMA , *PLASMODIUM , *APICOMPLEXA - Abstract
A modular approach to synthesize anti-Apicomplexa parasite inhibitors was developed that takes advantage of a pluripotent cyclic tetrapeptide scaffold capable of adjusting appendage and skeletal diversities in only a few steps (one to three steps). The diversification processes make use of selective radical coupling reactions and involve a new example of a reductive carbon-nitrogen cleavage reaction with SmI2. The resulting bioactive cyclic peptides have revealed new insights into structural factors that govern selectivity between Apicomplexa parasites such as Toxoplasma and Plasmodium and human cells. [ABSTRACT FROM AUTHOR]
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- 2013
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- View/download PDF
10. Rapamycin-sensitive signals control TCR/CD28-driven Ifng, Il4 and Foxp3 transcription and promoter region methylation.
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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]
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- 2011
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11. A Large Fraction of Extragenic RNA Pol II Transcription Sites Overlap Enhancers.
- Author
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De Santa, Francesca, Barozzi, Iros, Mietton, Flore, Ghisletti, Serena, Polletti, Sara, Tusi, Betsabeh Khoramian, Muller, Heiko, Ragoussis, Jiannis, Chia-Lin Wei, and Natoli, Gioacchino
- Abstract
Mammalian genomes are pervasively transcribed outside mapped protein-coding genes. One class of extragenic transcription products is represented by long non-coding RNAs (lncRNAs), some of which result from Pol_II transcription of bona-fide RNA genes. Whether all lncRNAs described insofar are products of RNA genes, however, is still unclear. Here we have characterized transcription sites located outside protein-coding genes in a highly regulated response, macrophage activation by endotoxin. Using chromatin signatures, we could unambiguously classify extragenic Pol_II binding sites as belonging to either canonical RNA genes or transcribed enhancers. Unexpectedly, 70% of extragenic Pol_II peaks were associated with genomic regions with a canonical chromatin signature of enhancers. Enhancer-associated extragenic transcription was frequently adjacent to inducible inflammatory genes, was regulated in response to endotoxin stimulation, and generated very low abundance transcripts. Moreover, transcribed enhancers were under purifying selection and contained binding sites for inflammatory transcription factors, thus suggesting their functionality. These data demonstrate that a large fraction of extragenic Pol_II transcription sites can be ascribed to cis-regulatory genomic regions. Discrimination between lncRNAs generated by canonical RNA genes and products of transcribed enhancers will provide a framework for experimental approaches to lncRNAs and help complete the annotation of mammalian genomes. [ABSTRACT FROM AUTHOR]
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- 2010
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12. Weak but Uniform Enrichment of the Histone Variant macroH2A1 along the Inactive X Chromosome.
- Author
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Mietton, Flore, Sengupta, Aditya K., Molla, Annie, Picchi, Gisele, Barral, Sophie, Heliot, Laurent, Grange, Thierry, Wutz, Anton, and Dimitrov, Stefan
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HISTONES , *CHROMOSOMES , *GREEN fluorescent protein , *MOLECULAR biology , *BIOCHEMISTRY education , *CHROMATIN , *PROTEIN microarrays - Abstract
We studied the enrichment and distribution of the histone variant mH2A1 in the condensed inactive X (Xi) chromosome. By using highly specific antibodies against mH2A1 and stable HEK 293 cell lines expressing either green fluorescent protein (GFP)-mH2A1 or GFP-H2A, we found that the Xi chromosome contains ∼1.5-fold more mH2A1 than the autosomes. To determine the in vivo distribution of mH2A1 along the X chromosome, we used a native chromatin immunoprecipitation-on-chip technique. DNA isolated from mH2A1-immunoprecipitated nucleosomes from either male or female mouse liver were hybridized to tiling microarrays covering 5 kb around most promoters or the entire X chromosome. The data show that mH2A1 is uniformly distributed across the entire Xi chromosome. Interestingly, a stronger mH2A1 enrichment along the pseudoautosomal X chromosome region was observed in both sexes. Our results indicate a potential role for macroH2A in large-scale chromosome structure and genome stability. [ABSTRACT FROM AUTHOR]
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- 2009
- Full Text
- View/download PDF
13. Nucleolin is a histone chaperone with FACT-like activity and assists remodeling of nucleosomes.
- Author
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Angelov, Dimitar, Bondarenko, Vladimir A., Almagro, Sébastien, Menoni, Hervé, Mongélard, Fabien, Hans, Fabienne, Mietton, Flore, Studitsky, Vasily M., Hamiche, Ali, Dimitrov, Stefan, and Bouvet, Philippe
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HISTONES ,MOLECULAR chaperones ,GENE expression ,GENETIC regulation ,CHROMATIN ,NUCLEOPROTEINS ,DNA-protein interactions - Abstract
Remodeling machines play an essential role in the control of gene expression, but how their activity is regulated is not known. Here we report that the nuclear protein nucleolin possesses a histone chaperone activity and that this factor greatly enhances the activity of the chromatin remodeling machineries SWI/SNF and ACF. Interestingly, nucleolin is able to induce the remodeling by SWI/SNF of macroH2A, but not of H2ABbd nucleosomes, which are otherwise resistant to remodeling. This new histone chaperone promotes the destabilization of the histone octamer, helping the dissociation of a H2A–H2B dimer, and stimulates the SWI/SNF-mediated transfer of H2A–H2B dimers. Furthermore, nucleolin facilitates transcription through the nucleosome, which is reminiscent of the activity of the FACT complex. This work defines new functions for histone chaperones in chromatin remodeling and regulation of transcription and explains how nucleolin could act on transcription. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
14. Selective BET bromodomain inhibition as an antifungal therapeutic strategy.
- Author
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Mietton, Flore, Ferri, Elena, Champleboux, Morgane, Zala, Ninon, Maubon, Danièle, Zhou, Yingsheng, Harbut, Mike, Spittler, Didier, Garnaud, Cécile, Courçon, Marie, Chauvel, Murielle, d'Enfert, Christophe, Kashemirov, Boris A., Hull, Mitchell, Cornet, Muriel, McKenna, Charles E., Govin, Jérôme, and Petosa, Carlo
- Abstract
Invasive fungal infections cause significant morbidity and mortality among immunocompromised individuals, posing an urgent need for new antifungal therapeutic strategies. Here we investigate a chromatin-interacting module, the bromodomain (BD) from the BET family of proteins, as a potential antifungal target in Candida albicans, a major human fungal pathogen. We show that the BET protein Bdf1 is essential in C. albicans and that mutations inactivating its two BDs result in a loss of viability in vitro and decreased virulence in mice. We report small-molecule compounds that inhibit C. albicans Bdf1 with high selectivity over human BDs. Crystal structures of the Bdf1 BDs reveal binding modes for these inhibitors that are sterically incompatible with the human BET-binding pockets. Furthermore, we report a dibenzothiazepinone compound that phenocopies the effects of a Bdf1 BD-inactivating mutation on C. albicans viability. These findings establish BET inhibition as a promising antifungal therapeutic strategy and identify Bdf1 as an antifungal drug target that can be selectively inhibited without antagonizing human BET function. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
15. Mechanism of Polymerase II Transcription Repression by the Histone Variant macroH2A.
- Author
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Doyen, Cécile-Marie, Woojin An, Angelov, Dimitar, Bondarenko, Vladimir, Mietton, Flore, Studitsky, Vassily M., Hamiche, Ali, Roeder, Robert G., Bouvet, Philippe, and Dimitrov, Stefan
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HISTONES ,DNA polymerases ,GENETIC transcription ,GENES ,CHROMATIN ,ACETYLATION - Abstract
macroH2A (mH2A) is an unusual histone variant consisting of a histone H2A-like domain fused to a large nonhistone region. In this work, we show that histone mH2A represses p300- and Gal4-VP16-dependent polymerase II transcription, and we have dissected the mechanism by which this repression is realized. The repressive effect of mH2A is observed at the level of initiation but not at elongation of transcription, and mH2A interferes with p300-dependent histone acetylation. The nonhistone region of mH2A is responsible for both the repression of initiation of transcription and the inhibition of histone acetylation. In addition, the presence of this domain of mH2A within the nucleosome is able to block nucleosome remodeling and sliding of the histone octamer to neighboring DNA segments by the remodelers SWI/SNF and ACF. These data unambiguously identify mH2A as a strong transcriptional repressor and show that the repressive effect of mH2A is realized on at least two different transcription activation chromatin-dependent pathways: histone acetylation and nucleosome remodeling. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
16. The histone variant mH2A1.1 interferes with transcription by down-regulating PARP-1 enzymatic activity.
- Author
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Ouararhni, Khalid, Hadj-Slimane, Réda, Ait-Si-Ali, Slimane, Robin, Philippe, Mietton, Flore, Harel-Bellan, Annick, Dimitrov, Stefan, and Hamiche, Ali
- Subjects
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HISTONES , *CHROMATIN , *ENZYMATIC analysis , *GENETIC transcription , *PROMOTERS (Genetics) , *ADENOSINE diphosphate - Abstract
The histone variant mH2A is believed to be involved in transcriptional repression, but how it exerts its function remains elusive. By using chromatin immunoprecipitation and tandem affinity immunopurification of the mH2A1.1 nucleosome complex, we identified numerous genes with promoters containing mH2A1.1 nucleosomes. In particular, the promoters of the inducible Hsp70.1 and Hsp70.2 genes, but not that of the constitutively expressed Hsp70.8, were highly enriched in mH2A1.1. PARP-1 was identified as a part of the mH2A1.1 nucleosome complex and was found to be associated with the Hsp70.1 promoter. A specific interaction between mH2A1.1 and PARP-1 was demonstrated and found to be associated with inactivation of PARP-1 enzymatic activity. Heat shock released both mH2A1.1 and PARP-1 from the Hsp70.1 promoter and activated PARP-1 automodification activity. The data we present point to a novel mechanism for control of Hsp70.1 gene transcription. mH2A1.1 recruits PARP-1 to the promoter, thereby inactivating it. Upon heat shock, the Hsp70.1 promoter-bound PARP-1 is released to activate transcription through ADP-ribosylation of other Hsp70.1 promoter-bound proteins. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
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