| First Author | Suh HC | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Pages | 46440 | PubMed ID | 28440307 |
| Mgi Jnum | J:315926 | Mgi Id | MGI:6831986 |
| Doi | 10.1038/srep46440 | Citation | Suh HC, et al. (2017) LPS independent activation of the pro-inflammatory receptor Trem1 by C/EBPepsilon in granulocytes. Sci Rep 7:46440 |
| abstractText | C/EBPepsilon is a critical transcriptional factor for granulocyte differentiation and function. Individuals with germline mutations of C/EBPepsilon fail to develop normal granulocytes and suffer from repeated infections. In order to gain a global view of the transcriptional machinery regulated by C/EBPepsilon, we performed whole-genome ChIP-Seq using mouse bone marrow cells. To complement the C/EBPepsilon DNA binding analyses, RNA-Sequencing was done in parallel using sorted mature and immature granulocytes from WT and C/EBPepsilon KO bone marrow. This approach led to the identification of several direct targets of C/EBPepsilon, which are potential effectors of its role in granulocytic differentiation and function. Interestingly, Trem1, a gene critical to granulocyte function, was identified as a direct C/EBPepsilon target gene. Trem1 expression overlaps very closely with expression signature of C/EBPepsilon during hematopoietic development. Luciferase reporter and EMSA assays revealed that C/EBPepsilon binds to the regulatory elements of Trem1 and regulates its expression during granulocytic differentiation. In addition, we provide evidence that inflammatory stimuli (LPS) can also control the expression of Trem1 independent of C/EBPepsilon. Overall, this study provides comprehensive profiling of the transcriptional network controlled by C/EBPepsilon during granulopoiesis and identifies Trem1 as one of its downstream effectors involved in eliciting an immune response. |
