title: Akirin specifies NF-κB selectivity of Drosophila innate immune response via chromatin remodeling.
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.
authors.affiliation: UPR9022 du CNRS, Institut de Biologie Moléculaire et Cellulaire Université de Strasbourg, Strasbourg Cedex, France.
authors.forename: François
authors.initials: F
authors.lastname: Bonnay
authors.affiliation: UPR9022 du CNRS, Institut de Biologie Moléculaire et Cellulaire Université de Strasbourg, Strasbourg Cedex, France.
authors.forename: Xuan-Hung
authors.initials: XH
authors.lastname: Nguyen
authors.affiliation: UPR9022 du CNRS, Institut de Biologie Moléculaire et Cellulaire Université de Strasbourg, Strasbourg Cedex, France.
authors.forename: Eva
authors.initials: E
authors.lastname: Cohen-Berros
authors.affiliation: UPR9022 du CNRS, Institut de Biologie Moléculaire et Cellulaire Université de Strasbourg, Strasbourg Cedex, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Troxler
authors.affiliation: Département de Biologie du Développement, Institut Pasteur, CNRS URA2578, Unité de Régulation Epigénétique, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Batsche
authors.affiliation: Institut Curie INSERM U-528, Paris Cedex, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Camonis
authors.affiliation: Laboratory of Infection and Prevention, Institute for Virus Research Kyoto University CREST, JST, Sakyo-ku, Kyoto, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.affiliation: UPR9022 du CNRS, Institut de Biologie Moléculaire et Cellulaire Université de Strasbourg, Strasbourg Cedex, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Reichhart
authors.affiliation: UPR9022 du CNRS, Institut de Biologie Moléculaire et Cellulaire Université de Strasbourg, Strasbourg Cedex, France n.matt@unistra.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Matt
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D007113:Immunity, Innate; D008297:Male; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D040901:Proteomics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
chemical_list: C462944:Bap60 protein, Drosophila; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; C101626:Rel protein, Drosophila; D015534:Trans-Activators; D014157:Transcription Factors; C526726:akirin protein, Drosophila; C086469:brm protein, Drosophila; C117995:osa protein, Drosophila
keywords: Chromatin remodeling; Drosophila; Innate immune response; NF‐κB