Format

Send to

Choose Destination
Oncotarget. 2017 Jan 17;8(3):5111-5122. doi: 10.18632/oncotarget.13872.

Macrophage production and activation are dependent on TRIM33.

Gallouet AS1,2,3,4,5, Ferri F1,2,3,4,5,6, Petit V1,2,3,4,5, Parcelier A1,2,3,4,5, Lewandowski D1,2,3,4,5, Gault N1,2,3,4,5, Barroca V1,2,3,4,5, Le Gras S6, Soler E1,2,3,4,7, Grosveld F7, Davidson I6, Romeo PH1,2,3,4,5.

Author information

1
CEA/DRF/iRCM/LRTS, 92265 Fontenay-aux-Roses cedex, France.
2
Inserm U967, 92265 Fontenay-aux-Roses cedex, France.
3
Université Paris-Diderot, Paris 7, France.
4
Université Paris-Sud, Paris 11, France.
5
Equipe labellisée Ligue contre le Cancer, France.
6
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.
7
Department of Cell Biology, Erasmus Medical Center, DR Molenwaterplein 50, 3015GE, Rotterdam, The Netherlands.

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.

KEYWORDS:

PU.1; TRIM33; inflammation; macrophage; myeloid differentiation

PMID:
27974684
PMCID:
PMC5354896
DOI:
10.18632/oncotarget.13872
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center