Macrophage production and activation are dependent on TRIM33
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Anne-Sophie Gallouet1,2,3,4,5, Federica Ferri1,2,3,4,5,6,*, Vanessa Petit1,2,3,4,5,*, Aude Parcelier1,2,3,4,5, Daniel Lewandowski1,2,3,4,5, Nathalie Gault1,2,3,4,5, Vilma Barroca1,2,3,4,5, Stéphanie Le Gras6, Eric Soler1,2,3,4,7, Frank Grosveld7, Irwin Davidson6, Paul-Henri Romeo1,2,3,4,5
1CEA/DRF/iRCM/LRTS, 92265 Fontenay-aux-Roses cedex, France
2Inserm U967, 92265 Fontenay-aux-Roses cedex, France
3Université Paris-Diderot, Paris 7, France
4Université Paris-Sud, Paris 11, France
5Equipe labellisée Ligue contre le Cancer, France
6Department 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
7Department of Cell Biology, Erasmus Medical Center, DR Molenwaterplein 50, 3015GE, Rotterdam, The Netherlands
*These authors have contributed equally to this work
Paul-Henri Romeo, email: [email protected]
Keywords: TRIM33, PU.1, macrophage, inflammation, myeloid differentiation
Received: June 07, 2016 Accepted: November 12, 2016 Published: December 10, 2016
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.
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