M3i

@article{bonnay_akirin_2014,

title = {Akirin specifies NF-κB selectivity of Drosophila innate immune response via chromatin remodeling},

author = {François Bonnay and Xuan-Hung Nguyen and Eva Cohen-Berros and Laurent Troxler and Eric Batsche and Jacques Camonis and Osamu Takeuchi and Jean-Marc Reichhart and Nicolas Matt},

doi = {10.15252/embj.201488456},

issn = {1460-2075},

year  = {2014},

date = {2014-10-01},

journal = {EMBO J.},

volume = {33},

number = {20},

pages = {2349--2362},

abstract = {The network of NF-κB-dependent transcription that activates both pro- and anti-inflammatory genes in mammals is still unclear. As NF-κB factors are evolutionarily conserved, we used Drosophila to understand this network. The NF-κB transcription factor Relish activates effector gene expression following Gram-negative bacterial immune challenge. Here, we show, using a genome-wide approach, that the conserved nuclear protein Akirin is a NF-κB co-factor required for the activation of a subset of Relish-dependent genes correlating with the presence of H3K4ac epigenetic marks. A large-scale unbiased proteomic analysis revealed that Akirin orchestrates NF-κB transcriptional selectivity through the recruitment of the Osa-containing-SWI/SNF-like Brahma complex (BAP). Immune challenge in Drosophila shows that Akirin is required for the transcription of a subset of effector genes, but dispensable for the transcription of genes that are negative regulators of the innate immune response. Therefore, Akirins act as molecular selectors specifying the choice between subsets of NF-κB target genes. The discovery of this mechanism, conserved in mammals, paves the way for the establishment of more specific and less toxic anti-inflammatory drugs targeting pro-inflammatory genes.},

keywords = {Animals, bioinformatic, Cell Cycle Proteins, Chromatin Assembly and Disassembly, chromatin remodeling, DNA-Binding Proteins, Female, Genetic, Immunity, Innate, Innate immune response, M3i, Male, matt, Mutation, NF-kappa B, NF‐κB, Promoter Regions, proteomics, reichhart, Trans-Activators, Transcription Factors, Transcriptional Activation, Two-Hybrid System Techniques},

pubstate = {published},

tppubtype = {article}

}

@article{tartey_akirin2_2014,

title = {Akirin2 is critical for inducing inflammatory genes by bridging IκB-ζ and the SWI/SNF complex},

author = {Sarang Tartey and Kazufumi Matsushita and Alexis Vandenbon and Daisuke Ori and Tomoko Imamura and Takashi Mino and Daron M Standley and Jules A Hoffmann and Jean-Marc Reichhart and Shizuo Akira and Osamu Takeuchi},

doi = {10.15252/embj.201488447},

issn = {1460-2075},

year  = {2014},

date = {2014-10-01},

journal = {EMBO J.},

volume = {33},

number = {20},

pages = {2332--2348},

abstract = {Transcription of inflammatory genes in innate immune cells is coordinately regulated by transcription factors, including NF-κB, and chromatin modifiers. However, it remains unclear how microbial sensing initiates chromatin remodeling. Here, we show that Akirin2, an evolutionarily conserved nuclear protein, bridges NF-κB and the chromatin remodeling SWI/SNF complex by interacting with BRG1-Associated Factor 60 (BAF60) proteins as well as IκB-ζ, which forms a complex with the NF-κB p50 subunit. These interactions are essential for Toll-like receptor-, RIG-I-, and Listeria-mediated expression of proinflammatory genes including Il6 and Il12b in macrophages. Consistently, effective clearance of Listeria infection required Akirin2. Furthermore, Akirin2 and IκB-ζ recruitment to the Il6 promoter depend upon the presence of IκB-ζ and Akirin2, respectively, for regulation of chromatin remodeling. BAF60 proteins were also essential for the induction of Il6 in response to LPS stimulation. Collectively, the IκB-ζ-Akirin2-BAF60 complex physically links the NF-κB and SWI/SNF complexes in innate immune cell activation. By recruiting SWI/SNF chromatin remodellers to IκB-ζ, transcriptional coactivator for NF-κB, the conserved nuclear protein Akirin2 stimulates pro-inflammatory gene promoters in mouse macrophages during innate immune responses to viral or bacterial infection.},

keywords = {Adaptor Proteins, Animals, Cell Nucleus, Chromatin Assembly and Disassembly, chromatin remodeling, Chromosomal Proteins, cytokine, Cytokines, Female, Gene Expression Regulation, gene regulation, Genetic, hoffmann, Humans, Immunity, Innate, innate immunity, Knockout, Listeria monocytogenes, M3i, Macrophages, Male, Mice, Multiprotein Complexes, Non-Histone, Nuclear Proteins, Promoter Regions, Protein Binding, reichhart, Repressor Proteins, Sequence Deletion, Signal Transducing, Transcriptional Activation},

pubstate = {published},

tppubtype = {article}

}

@article{zhang_asparaginyl_2010,

title = {The asparaginyl hydroxylase factor inhibiting HIF-1alpha is an essential regulator of metabolism.},

author = {Na Zhang and Zhenxing Fu and Sarah Linke and Johana Chicher and Jeffrey J Gorman and DeeAnn Visk and Gabriel G Haddad and Lorenz Poellinger and Daniel J Peet and Frank Powell and Randall S Johnson},

doi = {10.1016/j.cmet.2010.03.001},

issn = {1932-7420 1550-4131 1550-4131},

year  = {2010},

date = {2010-01-01},

journal = {Cell metabolism},

volume = {11},

number = {5},

pages = {364--378},

abstract = {Factor inhibiting HIF-1alpha (FIH) is an asparaginyl hydroxylase. Hydroxylation of HIF-alpha proteins by FIH blocks association of HIFs with the transcriptional coactivators CBP/p300, thus inhibiting transcriptional activation. We have created mice with a null mutation in the FIH gene and found that it has little or no discernable role in mice in altering classical aspects of HIF function, e.g., angiogenesis, erythropoiesis, or development. Rather, it is an essential regulator of metabolism: mice lacking FIH exhibit reduced body weight, elevated metabolic rate, hyperventilation, and improved glucose and lipid homeostasis and are resistant to high-fat-diet-induced weight gain and hepatic steatosis. Neuron-specific loss of FIH phenocopied some of the major metabolic phenotypes of the global null animals: those mice have reduced body weight, increased metabolic rate, and enhanced insulin sensitivity and are also protected against high-fat-diet-induced weight gain. These results demonstrate that FIH acts to a significant degree through the nervous system to regulate metabolism.},

keywords = {alpha Subunit/*antagonists & inhibitors/genetics, Animals, Asparagine/genetics/metabolism, Dietary Fats/pharmacology, Fatty Liver/etiology, Glucose/metabolism, Hyperventilation/etiology, Hypoxia-Inducible Factor 1, Insulin/metabolism, Knockout, Lipid Metabolism, Mice, Mixed Function Oxygenases/deficiency/genetics/*metabolism, PPSE, Transcriptional Activation, Weight Gain},

pubstate = {published},

tppubtype = {article}

}

@article{partidos_immunomodulatory_2009,

title = {Immunomodulatory consequences of ODN CpG-polycation complexes},

author = {Charalambos D Partidos and Johan Hoebeke and Sébastien Wieckowski and Olivier Chaloin and Alberto Bianco and Emmanuel Moreau and Jean-Paul Briand and Claude Desgranges and Sylviane Muller},

doi = {10.1016/j.ymeth.2009.03.005},

issn = {1095-9130},

year  = {2009},

date = {2009-12-01},

journal = {Methods (San Diego, Calif.)},

volume = {49},

number = {4},

pages = {328--333},

abstract = {Immunostimulatory ODN CpGs have extensively been tested as adjuvants and immunotherapeutics and hold a lot of promise for human use. In our studies we took advantage of their negative charge to study their biological activities after being complexed with carbon nanotubes, a novel vector for vaccine delivery and Tat protein of HIV, a target protein for therapeutic or prophylactic intervention. In the case of carbon nanotubes, ODN CpGs were able to form stable complexes based on charge interaction and exert increased immunostimulatory activity in vitro. With regard to the Tat protein, ODN CpGs were shown to bind effectively through the basic domain of the protein representing residues 44-61. Moreover, using surface Plasmon Resonance Technology and an in vitro cellular system, ODN CpGs were shown to inhibit the interaction of Tat protein with the transactivation responsive element, a bulged RNA hairpin structure. However, when ODN CpGs were complexed with Tat they readily increased the apoptotic properties of this protein as studied in CD3-stimulated Jurkat cells. Overall, our findings together with published data support the view that for harnessing the beneficial effects of ODN CpGs a careful consideration has to be given depending on the target intervention.},

keywords = {Animals, carbon, CpG Islands, Humans, I2CT, Immunologic Factors, Nanotubes, Oligodeoxyribonucleotides, Polyamines, Team-Bianco, Transcriptional Activation},

pubstate = {published},

tppubtype = {article}

}

@article{barillas-mury_immune_1996,

title = {Immune factor Gambif1, a new rel family member from the human malaria vector, Anopheles gambiae},

author = {Carolina Barillas-Mury and A Charlesworth and I Gross and A Richman and Jules A Hoffmann and Fotis C Kafatos},

issn = {0261-4189},

year  = {1996},

date = {1996-09-01},

journal = {EMBO J.},

volume = {15},

number = {17},

pages = {4691--4701},

abstract = {A novel rel family member, Gambif1 (gambiae immune factor 1), has been cloned from the human malaria vector, Anopheles gambiae, and shown to be most similar to Drosophila Dorsal and Dif. Gambif1 protein is translocated to the nucleus in fat body cells in response to bacterial challenge, although the mRNA is present at low levels at all developmental stages and is not induced by infection. DNA binding activity to the kappaB-like sites in the A.gambiae Defensin and the Drosophila Diptericin and Cecropin promoters is also induced in larval nuclear extracts following infection. Gambif1 has the ability to bind to kappaB-like sites in vitro. Co-transfection assays in Drosophila mbn-2 cells show that Gambif1 can activate transcription by interacting with the Drosophila Diptericin regulatory elements, but is not functionally equivalent to Dorsal in this assay. Gambif1 protein translocation to the nucleus and the appearance of kappaB-like DNA binding activity can serve as molecular markers of activation of the immune system and open up the possibility of studying the role of defence reactions in determining mosquito susceptibility/refractoriness to malaria infection.},

keywords = {Amino Acid, Animals, Anopheles, Base Sequence, Biological Transport, Cell Nucleus, Cells, Complementary, Cultured, DNA, DNA-Binding Proteins, hoffmann, Insect Proteins, Insect Vectors, M3i, NF-kappa B, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-rel, Sequence Homology, Trans-Activators, Transcriptional Activation},

pubstate = {published},

tppubtype = {article}

}

@article{gross_drosophila_1996,

title = {Drosophila immunity: a comparative analysis of the Rel proteins dorsal and Dif in the induction of the genes encoding diptericin and cecropin},

author = {I Gross and Philippe Georgel and Christine Kappler and Jean-Marc Reichhart and Jules A Hoffmann},

issn = {0305-1048},

year  = {1996},

date = {1996-04-01},

journal = {Nucleic Acids Res.},

volume = {24},

number = {7},

pages = {1238--1245},

abstract = {In Drosophila, bacterial challenge induces the rapid transcription of several genes encoding potent antibacterial peptides. The upstream sequences of the diptericin and cecropin Al genes, which have been investigated in detail, contain two, respectively one sequence element homologous to the binding site of the mammalian nuclear factor kappaB. These elements have been shown to be mandatory for immune-induced transcription of both genes. Functional studies have shown that these kappaB-related elements can be the target for the Drosophila Rel proteins dorsal and Dif. Here we present a comparative analysis of the transactivating capacities of these proteins on reporter genes fused to either the diptericin or the cecropin kappaB-related motifs. We conclude from our results: (i) the kappaB motifs of the diptericin and cecropin genes are not functionally equivalent; (ii) the dorsal and Dif proteins have distinct DNA-binding characteristics; (iii) dorsal and Dif can heterodimerize in vitro; (iv) mutants containing no copies of dorsal and a single copy of Dif retain their full capacity to express the diptericin and cecropin genes in response to challenge.},

keywords = {Animals, Antimicrobial Cationic Peptides, Base Sequence, DNA Primers, DNA-Binding Proteins, Gene Expression Regulation, Genetic, hoffmann, Insect Hormones, Insect Proteins, M3i, NF-kappa B, Nuclear Proteins, Peptides, Phosphoproteins, reichhart, Transcription, Transcription Factors, Transcriptional Activation},

pubstate = {published},

tppubtype = {article}

}