TRIM33 switches off Ifnb1 gene transcription during the late phase of macrophage activation

Federica Ferri, Aude Parcelier, Vanessa Petit, Anne-Sophie Gallouet, Daniel Lewandowski, Marion Dalloz, Anita van den Heuvel, Petros Kolovos, Eric Soler, Mario Leonardo Squadrito, Michele De Palma, Irwin Davidson (), Germain Rousselet () and Paul-Henri Romeo ()
Additional contact information
Federica Ferri: CEA/DSV/iRCM/LRTS, 18 route du Panorama
Aude Parcelier: CEA/DSV/iRCM/LRTS, 18 route du Panorama
Vanessa Petit: CEA/DSV/iRCM/LRTS, 18 route du Panorama
Anne-Sophie Gallouet: CEA/DSV/iRCM/LRTS, 18 route du Panorama
Daniel Lewandowski: CEA/DSV/iRCM/LRTS, 18 route du Panorama
Marion Dalloz: CEA/DSV/iRCM/LRTS, 18 route du Panorama
Anita van den Heuvel: Erasmus Medical Center
Petros Kolovos: Erasmus Medical Center
Eric Soler: CEA/DSV/iRCM/LRTS, 18 route du Panorama
Mario Leonardo Squadrito: The Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences École Polytechnique Fédérale de Lausanne (EPFL)
Michele De Palma: The Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences École Polytechnique Fédérale de Lausanne (EPFL)
Irwin Davidson: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP
Germain Rousselet: CEA/DSV/iRCM/LRTS, 18 route du Panorama
Paul-Henri Romeo: CEA/DSV/iRCM/LRTS, 18 route du Panorama

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: 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.

Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9900

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DOI: 10.1038/ncomms9900

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