title: Macrophage production and activation are dependent on TRIM33.
abstract: The tripartite motif (TRIM) family of proteins plays important roles in innate immunity and antimicrobial infection. None of these proteins has been shown to directly regulate transcription of genes in monocyte/macrophage except TRIM33 that we have recently shown to be a macrophage specific transcriptional inhibitor of Ifnb1. Using ChIP-seq analyses, we now report that TRIM33 is bound to two fold more genes in immature than in mature myeloid cell lines. When located near the same genes, TRIM33 is bound to different sequences in the two cell lines suggesting a role of TRIM33 in both immature and mature myeloid cells. Accordingly, expression of TRIM33 in immature myeloid cells is necessary for efficient production of small peritoneal macrophages, monocytes and bone marrow derived macrophage (BMDM) and TRIM33 targets a subset of genes involved in the inflammatory response only in mature myeloid cells. Functionally, this targeting is associated with impaired repression of pathways regulating the late phases of lipopolysaccharide (LPS) activation of BMDM and a high sensitivity to LPS in vivo when the trim33 gene is inactivated in mature myeloid cells. These findings pinpoint TRIM33 as an important transcriptional actor of monocyte/macrophage mediated inflammation.
authors.affiliation: CEA/DRF/iRCM/LRTS, 92265 Fontenay-aux-Roses cedex, France.|Inserm U967, 92265 Fontenay-aux-Roses cedex, France.|Université Paris-Diderot, Paris 7, France.|Université Paris-Sud, Paris 11, France.|Equipe labellisée Ligue contre le Cancer, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Gallouet
authors.affiliation: CEA/DRF/iRCM/LRTS, 92265 Fontenay-aux-Roses cedex, France.|Inserm U967, 92265 Fontenay-aux-Roses cedex, France.|Université Paris-Diderot, Paris 7, France.|Université Paris-Sud, Paris 11, France.|Equipe labellisée Ligue contre le Cancer, France.|Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 163, 67404 Illkirch Cedex, C. U. Strasbourg, France.
authors.forename: Federica
authors.initials: F
authors.lastname: Ferri
authors.affiliation: CEA/DRF/iRCM/LRTS, 92265 Fontenay-aux-Roses cedex, France.|Inserm U967, 92265 Fontenay-aux-Roses cedex, France.|Université Paris-Diderot, Paris 7, France.|Université Paris-Sud, Paris 11, France.|Equipe labellisée Ligue contre le Cancer, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Petit
authors.affiliation: CEA/DRF/iRCM/LRTS, 92265 Fontenay-aux-Roses cedex, France.|Inserm U967, 92265 Fontenay-aux-Roses cedex, France.|Université Paris-Diderot, Paris 7, France.|Université Paris-Sud, Paris 11, France.|Equipe labellisée Ligue contre le Cancer, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Parcelier
authors.affiliation: CEA/DRF/iRCM/LRTS, 92265 Fontenay-aux-Roses cedex, France.|Inserm U967, 92265 Fontenay-aux-Roses cedex, France.|Université Paris-Diderot, Paris 7, France.|Université Paris-Sud, Paris 11, France.|Equipe labellisée Ligue contre le Cancer, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lewandowski
authors.affiliation: CEA/DRF/iRCM/LRTS, 92265 Fontenay-aux-Roses cedex, France.|Inserm U967, 92265 Fontenay-aux-Roses cedex, France.|Université Paris-Diderot, Paris 7, France.|Université Paris-Sud, Paris 11, France.|Equipe labellisée Ligue contre le Cancer, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gault
authors.affiliation: CEA/DRF/iRCM/LRTS, 92265 Fontenay-aux-Roses cedex, France.|Inserm U967, 92265 Fontenay-aux-Roses cedex, France.|Université Paris-Diderot, Paris 7, France.|Université Paris-Sud, Paris 11, France.|Equipe labellisée Ligue contre le Cancer, France.
authors.forename: Vilma
authors.initials: V
authors.lastname: Barroca
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 163, 67404 Illkirch Cedex, C. U. Strasbourg, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Le Gras
authors.affiliation: CEA/DRF/iRCM/LRTS, 92265 Fontenay-aux-Roses cedex, France.|Inserm U967, 92265 Fontenay-aux-Roses cedex, France.|Université Paris-Diderot, Paris 7, France.|Université Paris-Sud, Paris 11, France.|Department of Cell Biology, Erasmus Medical Center, DR Molenwaterplein 50, 3015GE, Rotterdam, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Soler
authors.affiliation: Department of Cell Biology, Erasmus Medical Center, DR Molenwaterplein 50, 3015GE, Rotterdam, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Grosveld
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 163, 67404 Illkirch Cedex, C. U. Strasbourg, France.
authors.forename: Irwin
authors.initials: I
authors.lastname: Davidson
authors.affiliation: CEA/DRF/iRCM/LRTS, 92265 Fontenay-aux-Roses cedex, France.|Inserm U967, 92265 Fontenay-aux-Roses cedex, France.|Université Paris-Diderot, Paris 7, France.|Université Paris-Sud, Paris 11, France.|Equipe labellisée Ligue contre le Cancer, France.
authors.forename: Paul-Henri
authors.initials: PH
authors.lastname: Romeo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000378:metabolism; D053263:Gene Regulatory Networks; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology; D000067996:RAW 264.7 Cells; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D008070:Lipopolysaccharides; D014157:Transcription Factors; C491420:Trim33 protein, mouse; D004247:DNA
keywords: PU.1; TRIM33; inflammation; macrophage; myeloid differentiation