title: TRIM33 switches off Ifnb1 gene transcription during the late phase of macrophage activation.
abstract: Despite its importance during viral or bacterial infections, transcriptional regulation of the interferon-β gene (Ifnb1) in activated macrophages is only partially understood. Here we report that TRIM33 deficiency results in high, sustained expression of Ifnb1 at late stages of toll-like receptor-mediated activation in macrophages but not in fibroblasts. In macrophages, TRIM33 is recruited by PU.1 to a conserved region, the Ifnb1 Control Element (ICE), located 15 kb upstream of the Ifnb1 transcription start site. ICE constitutively interacts with Ifnb1 through a TRIM33-independent chromatin loop. At late phases of lipopolysaccharide activation of macrophages, TRIM33 is bound to ICE, regulates Ifnb1 enhanceosome loading, controls Ifnb1 chromatin structure and represses Ifnb1 gene transcription by preventing recruitment of CBP/p300. These results characterize a previously unknown mechanism of macrophage-specific regulation of Ifnb1 transcription whereby TRIM33 is critical for Ifnb1 gene transcription shutdown.
authors.affiliation: CEA/DSV/iRCM/LRTS, 18 route du Panorama, Fontenay-aux-Roses 92265, France.|Inserm U967, Fontenay-aux-Roses 92265, France.|Université Paris-Diderot, Paris 75013, France.|Université Paris-Sud, Orsay 91400, France.|Equipe labellisée Ligue contre le Cancer, 18 route du Panorama, Fontenay-aux-Roses 92265, France.|Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 163, Strasbourg, Illkirch Cedex 67404, France.
authors.forename: Federica
authors.initials: F
authors.lastname: Ferri
authors.affiliation: CEA/DSV/iRCM/LRTS, 18 route du Panorama, Fontenay-aux-Roses 92265, France.|Inserm U967, Fontenay-aux-Roses 92265, France.|Université Paris-Diderot, Paris 75013, France.|Université Paris-Sud, Orsay 91400, France.|Equipe labellisée Ligue contre le Cancer, 18 route du Panorama, Fontenay-aux-Roses 92265, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Parcelier
authors.affiliation: CEA/DSV/iRCM/LRTS, 18 route du Panorama, Fontenay-aux-Roses 92265, France.|Inserm U967, Fontenay-aux-Roses 92265, France.|Université Paris-Diderot, Paris 75013, France.|Université Paris-Sud, Orsay 91400, France.|Equipe labellisée Ligue contre le Cancer, 18 route du Panorama, Fontenay-aux-Roses 92265, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Petit
authors.affiliation: CEA/DSV/iRCM/LRTS, 18 route du Panorama, Fontenay-aux-Roses 92265, France.|Inserm U967, Fontenay-aux-Roses 92265, France.|Université Paris-Diderot, Paris 75013, France.|Université Paris-Sud, Orsay 91400, France.|Equipe labellisée Ligue contre le Cancer, 18 route du Panorama, Fontenay-aux-Roses 92265, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Gallouet
authors.affiliation: CEA/DSV/iRCM/LRTS, 18 route du Panorama, Fontenay-aux-Roses 92265, France.|Inserm U967, Fontenay-aux-Roses 92265, France.|Université Paris-Diderot, Paris 75013, France.|Université Paris-Sud, Orsay 91400, France.|Equipe labellisée Ligue contre le Cancer, 18 route du Panorama, Fontenay-aux-Roses 92265, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lewandowski
authors.affiliation: CEA/DSV/iRCM/LRTS, 18 route du Panorama, Fontenay-aux-Roses 92265, France.|Inserm U967, Fontenay-aux-Roses 92265, France.|Université Paris-Diderot, Paris 75013, France.|Université Paris-Sud, Orsay 91400, France.|Equipe labellisée Ligue contre le Cancer, 18 route du Panorama, Fontenay-aux-Roses 92265, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Dalloz
authors.affiliation: Department of Cell Biology, Erasmus Medical Center, DR Molenwaterplein 50, Rotterdam 3015GE, The Netherlands.
authors.forename: Anita
authors.initials: A
authors.lastname: van den Heuvel
authors.affiliation: Department of Cell Biology, Erasmus Medical Center, DR Molenwaterplein 50, Rotterdam 3015GE, The Netherlands.
authors.forename: Petros
authors.initials: P
authors.lastname: Kolovos
authors.affiliation: CEA/DSV/iRCM/LRTS, 18 route du Panorama, Fontenay-aux-Roses 92265, France.|Inserm U967, Fontenay-aux-Roses 92265, France.|Université Paris-Diderot, Paris 75013, France.|Université Paris-Sud, Orsay 91400, France.|Department of Cell Biology, Erasmus Medical Center, DR Molenwaterplein 50, Rotterdam 3015GE, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Soler
authors.affiliation: The Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences École Polytechnique Fédérale de Lausanne (EPFL), Lausanne CH-1015, Switzerland.
authors.forename: Mario Leonardo
authors.initials: ML
authors.lastname: Squadrito
authors.affiliation: The Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences École Polytechnique Fédérale de Lausanne (EPFL), Lausanne CH-1015, Switzerland.
authors.forename: Michele
authors.initials: M
authors.lastname: De Palma
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 163, Strasbourg, Illkirch Cedex 67404, France.
authors.forename: Irwin
authors.initials: I
authors.lastname: Davidson
authors.affiliation: CEA/DSV/iRCM/LRTS, 18 route du Panorama, Fontenay-aux-Roses 92265, France.|Inserm U967, Fontenay-aux-Roses 92265, France.|Université Paris-Diderot, Paris 75013, France.|Université Paris-Sud, Orsay 91400, France.|Equipe labellisée Ligue contre le Cancer, 18 route du Panorama, Fontenay-aux-Roses 92265, France.
authors.forename: Germain
authors.initials: G
authors.lastname: Rousselet
authors.affiliation: CEA/DSV/iRCM/LRTS, 18 route du Panorama, Fontenay-aux-Roses 92265, France.|Inserm U967, Fontenay-aux-Roses 92265, France.|Université Paris-Diderot, Paris 75013, France.|Université Paris-Sud, Orsay 91400, France.|Equipe labellisée Ligue contre le Cancer, 18 route du Panorama, Fontenay-aux-Roses 92265, France.
authors.forename: Paul-Henri
authors.initials: PH
authors.lastname: Romeo
mesh_terms: D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D016899:Interferon-beta / Q000235:genetics* / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors; C491420:Trim33 protein, mouse; D016899:Interferon-beta