Publications
2014
Tartey Sarang, Matsushita Kazufumi, Vandenbon Alexis, Ori Daisuke, Imamura Tomoko, Mino Takashi, Standley Daron M, Hoffmann Jules A, Reichhart Jean-Marc, Akira Shizuo, Takeuchi Osamu
Akirin2 is critical for inducing inflammatory genes by bridging IκB-ζ and the SWI/SNF complex Journal Article
In: EMBO J., vol. 33, no. 20, pp. 2332–2348, 2014, ISSN: 1460-2075.
Abstract | Links | BibTeX | Tags: 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
@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}
}
Goto Akira, Fukuyama Hidehiro, Imler Jean-Luc, Hoffmann Jules A
In: The Journal of Biological Chemistry, vol. 289, no. 30, pp. 20470–20476, 2014, ISSN: 1083-351X.
Abstract | Links | BibTeX | Tags: Animals, Cell Line, Chromatin Assembly and Disassembly, Epistasis, Escherichia coli, Escherichia coli Infections, Genetic, hoffmann, imler, Immunity, Innate, M3i, NF-kappa B, Repressor Proteins, Signal Transduction, Transcription Factors
@article{goto_chromatin_2014,
title = {The chromatin regulator DMAP1 modulates activity of the nuclear factor B (NF-B) transcription factor Relish in the Drosophila innate immune response},
author = {Akira Goto and Hidehiro Fukuyama and Jean-Luc Imler and Jules A Hoffmann},
doi = {10.1074/jbc.C114.553719},
issn = {1083-351X},
year = {2014},
date = {2014-07-01},
journal = {The Journal of Biological Chemistry},
volume = {289},
number = {30},
pages = {20470--20476},
abstract = {The host defense of the model organism Drosophila is under the control of two major signaling cascades controlling transcription factors of the NF-B family, the Toll and the immune deficiency (IMD) pathways. The latter shares extensive similarities with the mammalian TNF-R pathway and was initially discovered for its role in anti-Gram-negative bacterial reactions. A previous interactome study from this laboratory reported that an unexpectedly large number of proteins are binding to the canonical components of the IMD pathway. Here, we focus on DNA methyltransferase-associated protein 1 (DMAP1), which this study identified as an interactant of Relish, a Drosophila transcription factor reminiscent of the mammalian p105 NF-B protein. We show that silencing of DMAP1 expression both in S2 cells and in flies results in a significant reduction of Escherichia coli-induced expression of antimicrobial peptides. Epistatic analysis indicates that DMAP1 acts in parallel or downstream of Relish. Co-immunoprecipitation experiments further reveal that, in addition to Relish, DMAP1 also interacts with Akirin and the Brahma-associated protein 55 kDa (BAP55). Taken together, these results reveal that DMAP1 is a novel nuclear modulator of the IMD pathway, possibly acting at the level of chromatin remodeling.},
keywords = {Animals, Cell Line, Chromatin Assembly and Disassembly, Epistasis, Escherichia coli, Escherichia coli Infections, Genetic, hoffmann, imler, Immunity, Innate, M3i, NF-kappa B, Repressor Proteins, Signal Transduction, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}
2010
Pospisilik Andrew J, Schramek Daniel, Schnidar Harald, Cronin Shane J F, Nehme Nadine T, Zhang Xiaoyun, Knauf Claude, Cani Patrice D, Aumayr Karin, Todoric Jelena, Bayer Martina, Haschemi Arvand, Puviindran Vijitha, Tar Krisztina, Orthofer Michael, Neely Gregory G, Dietzl Georg, Manoukian Armen, Funovics Martin, Prager Gerhard, Wagner Oswald, Ferrandon Dominique, Aberger Fritz, Hui Chi-chung, Esterbauer Harald, Penninger Josef M
Drosophila genome-wide obesity screen reveals hedgehog as a determinant of brown versus white adipose cell fate Journal Article
In: Cell, vol. 140, no. 1, pp. 148–160, 2010, ISSN: 1097-4172.
Abstract | Links | BibTeX | Tags: Adipocytes, Adipogenesis, Animals, Brown, Brown/metabolism, Cyclic AMP, Cyclic AMP/metabolism, Drosophila Proteins/*metabolism, ferrandon, Glucocorticoids, Glucocorticoids/metabolism, Hedgehog Proteins, Hedgehog Proteins/*metabolism, Humans, Knockout, M3i, Mice, Muscle Cells, Muscle Cells/metabolism, Obesity, Obesity/*genetics, Repressor Proteins, Repressor Proteins/genetics, White, White/metabolism
@article{pospisilik_drosophila_2010b,
title = {Drosophila genome-wide obesity screen reveals hedgehog as a determinant of brown versus white adipose cell fate},
author = {Andrew J Pospisilik and Daniel Schramek and Harald Schnidar and Shane J F Cronin and Nadine T Nehme and Xiaoyun Zhang and Claude Knauf and Patrice D Cani and Karin Aumayr and Jelena Todoric and Martina Bayer and Arvand Haschemi and Vijitha Puviindran and Krisztina Tar and Michael Orthofer and Gregory G Neely and Georg Dietzl and Armen Manoukian and Martin Funovics and Gerhard Prager and Oswald Wagner and Dominique Ferrandon and Fritz Aberger and Chi-chung Hui and Harald Esterbauer and Josef M Penninger},
doi = {10.1016/j.cell.2009.12.027},
issn = {1097-4172},
year = {2010},
date = {2010-01-01},
journal = {Cell},
volume = {140},
number = {1},
pages = {148--160},
abstract = {Over 1 billion people are estimated to be overweight, placing them at risk for diabetes, cardiovascular disease, and cancer. We performed a systems-level genetic dissection of adiposity regulation using genome-wide RNAi screening in adult Drosophila. As a follow-up, the resulting approximately 500 candidate obesity genes were functionally classified using muscle-, oenocyte-, fat-body-, and neuronal-specific knockdown in vivo and revealed hedgehog signaling as the top-scoring fat-body-specific pathway. To extrapolate these findings into mammals, we generated fat-specific hedgehog-activation mutant mice. Intriguingly, these mice displayed near total loss of white, but not brown, fat compartments. Mechanistically, activation of hedgehog signaling irreversibly blocked differentiation of white adipocytes through direct, coordinate modulation of early adipogenic factors. These findings identify a role for hedgehog signaling in white/brown adipocyte determination and link in vivo RNAi-based scanning of the Drosophila genome to regulation of adipocyte cell fate in mammals.},
keywords = {Adipocytes, Adipogenesis, Animals, Brown, Brown/metabolism, Cyclic AMP, Cyclic AMP/metabolism, Drosophila Proteins/*metabolism, ferrandon, Glucocorticoids, Glucocorticoids/metabolism, Hedgehog Proteins, Hedgehog Proteins/*metabolism, Humans, Knockout, M3i, Mice, Muscle Cells, Muscle Cells/metabolism, Obesity, Obesity/*genetics, Repressor Proteins, Repressor Proteins/genetics, White, White/metabolism},
pubstate = {published},
tppubtype = {article}
}
1994
Auble D T, Hansen K E, Mueller C G, Lane W S, Thorner J, Hahn S
Mot1, a global repressor of RNA polymerase II transcription, inhibits TBP binding to DNA by an ATP-dependent mechanism Journal Article
In: Genes & Development, vol. 8, no. 16, pp. 1920–1934, 1994, ISSN: 0890-9369.
Abstract | Links | BibTeX | Tags: Adenosine Triphosphatases, Adenosine Triphosphate, Amino Acid Sequence, Base Sequence, Biological, DNA, DNA Helicases, DNA Probes, DNA-Binding Proteins, Fungal, Fungal Proteins, Genes, Genetic, Models, Molecular Sequence Data, Mutagenesis, Repressor Proteins, RNA Polymerase II, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Site-Directed, TATA Box, TATA-Binding Protein Associated Factors, TATA-Box Binding Protein, Team-Mueller, Transcription, Transcription Factors
@article{auble_mot1_1994,
title = {Mot1, a global repressor of RNA polymerase II transcription, inhibits TBP binding to DNA by an ATP-dependent mechanism},
author = {D T Auble and K E Hansen and C G Mueller and W S Lane and J Thorner and S Hahn},
doi = {10.1101/gad.8.16.1920},
issn = {0890-9369},
year = {1994},
date = {1994-08-01},
journal = {Genes & Development},
volume = {8},
number = {16},
pages = {1920--1934},
abstract = {Basal transcription of many genes in yeast is repressed by Mot1, an essential protein which is a member of the Snf2/Swi2 family of conserved nuclear factors. ADI is an ATP-dependent inhibitor of TATA-binding protein (TBP) binding to DNA that inhibits transcription in vitro. Here we demonstrate that ADI is encoded by the MOT1 gene. Mutation of MOT1 abolishes ADI activity and derepresses basal transcription in vitro and in vivo. Recombinant Mot1 removes TBP from DNA and Mot1 contains an ATPase activity which is essential for its function. Genetic interactions between Mot1 and TBP indicate that their functions are interlinked in vivo. These results provide a general model for understanding the mechanism of action of a large family of nuclear factors involved in processes such as transcription and DNA repair.},
keywords = {Adenosine Triphosphatases, Adenosine Triphosphate, Amino Acid Sequence, Base Sequence, Biological, DNA, DNA Helicases, DNA Probes, DNA-Binding Proteins, Fungal, Fungal Proteins, Genes, Genetic, Models, Molecular Sequence Data, Mutagenesis, Repressor Proteins, RNA Polymerase II, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Site-Directed, TATA Box, TATA-Binding Protein Associated Factors, TATA-Box Binding Protein, Team-Mueller, Transcription, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}