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- W4313359910 abstract "Abstract An inducible program of inflammatory gene expression is a hallmark of antimicrobial defenses. This response is controlled by a collaboration involving signal-dependent activation of transcription factors, transcriptional co-regulators, and chromatin-modifying factors. Here we have identified a highly conserved Zinc finger DNA binding protein CNBP (also called ZNF9) upregulated in myeloid cells exposed to lipopolysaccharide. CNBP resides primarily in the cytosol and upon TLR4 engagement, CNBP translocate to the nucleus. To investigate the functional consequences of these events, we generated mice lacking CNBP and characterized the role of CNBP in controlling the inducible transcriptional program using a combination of RNA-sequencing and multiplex gene expression analysis (Nanostring). In response to an array of signals such as LPS, CNBP-deficient macrophages were impaired in their ability to induce important immune genes including IL12p40 and IL6 amongst others. CNBP-deficient cells showed normal activation of TBK1 and p65. However, the nuclear translocation of c-Rel that is critical for the inducible expression of IL-12p40 was significantly compromised in cells lacking CNBP. Furthermore, Chromatin Immunoprecipitation experiments revealed that CNBP itself bound the IL12 promoter and c-Rel binding to this promoter was compromised in CNBP-deficient macrophages. Lastly, ectopic expression of wild type CNBP but not a mutant form that could not be phosphorylated together with c-Rel led to synergistic activation of an IL12 promoter driven reporter gene. Collectively, these findings identify CNBP as a novel DNA binding protein that acts as a transcriptional regulator controlling the inflammatory program in macrophages." @default.
- W4313359910 created "2023-01-06" @default.
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- W4313359910 date "2017-05-01" @default.
- W4313359910 modified "2023-09-24" @default.
- W4313359910 title "Regulation of immune gene expression by the zinc finger DNA binding protein, CNBP/ZNF9" @default.
- W4313359910 doi "https://doi.org/10.4049/jimmunol.198.supp.70.11" @default.
- W4313359910 hasPublicationYear "2017" @default.
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