| First Author | Lennard Richard ML | Year | 2016 |
| Journal | Eur J Immunol | Volume | 46 |
| Issue | 10 | Pages | 2322-2332 |
| PubMed ID | 27431361 | Mgi Jnum | J:249782 |
| Mgi Id | MGI:5923262 | Doi | 10.1002/eji.201646315 |
| Citation | Lennard Richard ML, et al. (2016) Acetylation impacts Fli-1-driven regulation of granulocyte colony stimulating factor. Eur J Immunol 46(10):2322-2332 |
| abstractText | Fli-1 has emerged as a critical regulator of inflammatory mediators, including MCP-1, CCL5, and IL-6. The cytokine, granulocyte colony stimulating factor (G-CSF) regulates neutrophil precursor maturation and survival, and activates mature neutrophils. Previously, a significant decrease in neutrophil infiltration into the kidneys of Fli-1+/- lupus-prone mice was observed. In this study, a significant decrease in G-CSF protein expression was detected in stimulated murine and human endothelial cells when expression of Fli-1 was inhibited. The murine G-CSF promoter contains numerous putative Fli-1 binding sites and several regions within the proximal promoter are significantly enriched for Fli-1 binding. Transient transfection assays indicate that Fli-1 drives transcription from the G-CSF promoter and mutation of the Fli-1 DNA binding domain resulted in a 94% loss of transcriptional activation. Mutation of a known acetylation site, led to a significant increase in G-CSF promoter activation. The histone acetyltransferases p300/CBP and p300/CBP associated factor (PCAF) significantly decrease Fli-1 specific activation of the G-CSF promoter. Thus, acetylation appears to be an important mechanism behind Fli-1 driven activation of the G-CSF promoter. These results further support the theory that Fli-1 plays a major role in the regulation of several inflammatory mediators, ultimately affecting inflammatory disease pathogenesis. |
