Macrophage production and activation are dependent on TRIM33
Lipopolysaccharides
Chromatin Immunoprecipitation
EMC OR-01
Pu.1
macrophage
Trim33
Mice
03 medical and health sciences
Animals
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Gene Regulatory Networks
Myeloid Cells
Cells, Cultured
0303 health sciences
Macrophages
DNA
Sequence Analysis, DNA
Macrophage Activation
Chromatin
3. Good health
RAW 264.7 Cells
inflammation
myeloid differentiation
Research Paper
Transcription Factors
DOI:
10.18632/oncotarget.13872
Publication Date:
2016-12-10T20:24:35Z
AUTHORS (12)
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.
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CITATIONS (29)
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