title: Genome-wide Chromatin Profiling of Legionella pneumophila-Infected Human Macrophages Reveals Activation of the Probacterial Host Factor TNFAIP2.
abstract: Legionella pneumophila is a causative agent of severe pneumonia. Infection leads to a broad host cell response, as evident, for example, on the transcriptional level. Chromatin modifications, which control gene expression, play a central role in the transcriptional response to L. pneumophila
  
  
  
  We infected human-blood-derived macrophages (BDMs) with L. pneumophila and used chromatin immunoprecipitation followed by sequencing to screen for gene promoters with the activating histone 4 acetylation mark.
  
  
  
  We found the promoter of tumor necrosis factor α-induced protein 2 (TNFAIP2) to be acetylated at histone H4. This factor has not been characterized in the pathology of L. pneumophila TNFAIP2 messenger RNA and protein were upregulated in response to L. pneumophila infection of human-BDMs and human alveolar epithelial (A549) cells. We showed that L. pneumophila-induced TNFAIP2 expression is dependent on the NF-κB transcription factor. Importantly, knock down of TNFAIP2 led to reduced intracellular replication of L. pneumophila Corby in A549 cells.
  
  
  
  Taken together, genome-wide chromatin analysis of L. pneumophila-infected macrophages demonstrated induction of TNFAIP2, a NF-κB-dependent factor relevant for bacterial replication.
authors.affiliation: Institute for Lung Research/iLung Universities of Giessen and arburg Lung Centre, German Center for Lung Research.
authors.forename: Ilona
authors.initials: I
authors.lastname: Du Bois
authors.affiliation: Max Planck Institute for Molecular Genetics Free University, Berlin.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Marsico
authors.affiliation: Institute for Lung Research/iLung Universities of Giessen and arburg Lung Centre, German Center for Lung Research.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bertrams
authors.affiliation: Functional Epigenomics, University of Cologne.
authors.forename: Michal R
authors.initials: MR
authors.lastname: Schweiger
authors.affiliation: Max Planck Institute for Molecular Genetics.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Caffrey
authors.affiliation: Institute for Lung Research/iLung Universities of Giessen and arburg Lung Centre, German Center for Lung Research.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sittka-Stark
authors.affiliation: Laboratory of Systems Tumor Immunology, Department of Dermatology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Eberhardt
authors.affiliation: Laboratory of Systems Tumor Immunology, Department of Dermatology, Friedrich-Alexander University Erlangen-Nürnberg, University Hospital Erlangen, Germany.
authors.forename: Julio
authors.initials: J
authors.lastname: Vera
authors.affiliation: Max Planck Institute for Molecular Genetics.
authors.forename: Martin
authors.initials: M
authors.lastname: Vingron
authors.affiliation: Institute for Lung Research/iLung Department of Medicine, Pulmonary, and Critical Care Medicine, University Medical Center Marburg, Philipps-University Universities of Giessen and arburg Lung Centre, German Center for Lung Research.
authors.forename: Bernd T
authors.initials: BT
authors.lastname: Schmeck
mesh_terms: D000107:Acetylation; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry; D047369:Chromatin Immunoprecipitation; D016207:Cytokines / Q000032:analysis* / Q000235:genetics; D004847:Epithelial Cells / Q000737:chemistry / Q000382:microbiology; D006657:Histones / Q000032:analysis; D054884:Host-Pathogen Interactions; D006801:Humans; D016952:Legionella pneumophila / Q000472:pathogenicity*; D008264:Macrophages / Q000737:chemistry* / Q000382:microbiology*
chemical_list: D002843:Chromatin; D016207:Cytokines; D006657:Histones; C085839:TNFAIP2 protein, human
keywords: A549; Legionella pneumophila; TNFAIP2; macrophage