Trim33/Tif1γ is involved in late stages of granulomonopoiesis in mice

Chrétien, Marie‐Lorraine; Legouge, C.; Martin, Romain Z.; Hammann, Arlette; Trad, Malika; Aucagne, Romain; Largeot, Anne; Bastie, Jean-Noël; Delva, Laurent; Quéré, Ronan

doi:10.1016/j.exphem.2016.04.009

Cited by 16 publications

(18 citation statements)

References 42 publications

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“…This result is in accordance with a recent study that showed that Trim33 knock-out in hematopoietic cells results in abnormal monocyte and macrophage maturations associated with decreased expression of the CSF-1 receptor [17]. We did not find CSF1-R decreased expression in MxCre/ Trim33 −/− mice (data not shown) although TRIM33 peaks were present in the Csf1-R gene with one peak within the Csf1-R intronic enhancer [24] (Supplementary Figure S4B).…”

Section: Discussionsupporting

confidence: 93%

Macrophage production and activation are dependent on TRIM33

et al. 2016

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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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Section: Discussionsupporting

confidence: 93%

Macrophage production and activation are dependent on TRIM33

et al. 2016

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“…4a ). We then transduced ASXL1-MT and BAP1 into murine c-Kit + progenitor cells, and induced myeloid differentiation with various combinations of cytokines 21 , 25 , 26 . In the mast cell differentiation assay, ASXL1-MT alone modestly impaired mast cell maturation of murine HSPCs, and this inhibitory effect was enhanced by BAP1 coexpression.…”

Section: Resultsmentioning

confidence: 99%

Mutant ASXL1 cooperates with BAP1 to promote myeloid leukaemogenesis

et al. 2018

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ASXL1 mutations occur frequently in myeloid neoplasms and are associated with poor prognosis. However, the mechanisms by which mutant ASXL1 induces leukaemogenesis remain unclear. In this study, we report mutually reinforcing effects between a C-terminally truncated form of mutant ASXL1 (ASXL1-MT) and BAP1 in promoting myeloid leukaemogenesis. BAP1 expression results in increased monoubiquitination of ASXL1-MT, which in turn increases the catalytic function of BAP1. This hyperactive ASXL1-MT/BAP1 complex promotes aberrant myeloid differentiation of haematopoietic progenitor cells and accelerates RUNX1-ETO-driven leukaemogenesis. Mechanistically, this complex induces upregulation of posterior HOXA genes and IRF8 through removal of H2AK119 ubiquitination. Importantly, BAP1 depletion inhibits posterior HOXA gene expression and leukaemogenicity of ASXL1-MT-expressing myeloid leukemia cells. Furthermore, BAP1 is also required for the growth of MLL-fusion leukemia cells with posterior HOXA gene dysregulation. These data indicate that BAP1, which has long been considered a tumor suppressor, in fact plays tumor-promoting roles in myeloid neoplasms.

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“…It has been shown that TIF1γ participates in the differentiation of stem cells in collaboration with Smad4, by direct interaction with histone via PHD–bromodomain leading to the assembling of Smad4/Smad2–3 complex on targeted genes ( 101 ). In adult tissues, TIF1γ promotes the terminal differentiation of mammary gland and lactation by antagonization of Smad4 ( 102 ), supports both osteoblast proliferation and differentiation under stimulation of bone morphogenetic proteins (BMP) via the activation of a particular RSmad complex (Smad1/5) ( 103 ), regulates granulopoiesis in mice ( 104 ), and participates in the development of iNKT cells ( 105 ). During erythropoiesis, Smad4 and TIF1γ competitively bind to phosphorylated SMad2/3 (RSmad) in response to TGF-β to promote the proliferation and maturation of erythroblasts ( 106 , 107 ).…”

Section: Targets Of Cancer-associated Autoimmune Response In Myositismentioning

confidence: 99%

“…Next, TIF1γ is a strong tumor suppressor by preventing β-catenin degradation ( 116 ), epithelial-to-mesenchymal transition ( 117 , 118 ), and by regulation of the chromatin ( 119 , 120 ). The role of TIF1γ as a tumor suppressor has been directly shown in chronic myelomonocytic leukemia ( 121 ), pancreatic tumor ( 122 – 124 ), hepatocellular carcinoma ( 125 ), renal cell carcinoma ( 126 ), and non-small cell lung cancer ( 127 ), where TIF1γ decreased expression or inactivation promotes proliferation and probably epithelial-to-mesenchymal transition ( 97 – 104 ). Paradoxically, overexpression of TIF1γ is involved in oncogenesis notably in breast cancer, where TIF1γ interferes with TGF-β to promote poorer prognosis ( 128 ).…”

Section: Targets Of Cancer-associated Autoimmune Response In Myositismentioning

confidence: 99%

Dermatomyositis and Immune-Mediated Necrotizing Myopathies: A Window on Autoimmunity and Cancer

2017

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Autoimmune myopathies (myositides) are strongly associated with malignancy. The link between myositis and cancer, originally noticed by Bohan and Peter in their classification in 1975 (1), has been evidenced by large population-based cohort studies and a recent meta-analysis. The numerous reports of cases in which the clinical course of myositis reflects that of cancer and the short delay between myositis and cancer onset support the notion that myositis may be an authentic paraneoplastic disorder. Thus, cancer-associated myositis raises the question of cancer as a cause rather than a consequence of autoimmunity. Among myositides, dermatomyositis and more recently, although to a lesser extent, immune-mediated necrotizing myopathies are the most documented forms associated with cancer. Interestingly, the current diagnostic approach for myositis is based on the identification of specific antibodies where each antibody determines specific clinical features and outcomes. Recent findings have shown that the autoantibodies anti-TIF1γ, anti-NXP2 and anti-HMGCR are associated with cancers in the course of myositis. Herein, we highlight the fact that the targets of these three autoantibodies involve cellular pathways that intervene in tumor promotion and we discuss the role of cancer mutations as autoimmunity triggers in adult myositis.

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Trim33/Tif1γ is involved in late stages of granulomonopoiesis in mice

Cited by 16 publications

References 42 publications

Macrophage production and activation are dependent on TRIM33

Macrophage production and activation are dependent on TRIM33

Mutant ASXL1 cooperates with BAP1 to promote myeloid leukaemogenesis

Dermatomyositis and Immune-Mediated Necrotizing Myopathies: A Window on Autoimmunity and Cancer

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