| First Author | Zhang Y | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 737 |
| PubMed ID | 30679703 | Mgi Jnum | J:275918 |
| Mgi Id | MGI:6304905 | Doi | 10.1038/s41598-018-37402-z |
| Citation | Zhang Y, et al. (2019) Gfi1-Mediated Repression of c-Fos, Egr-1 and Egr-2, and Inhibition of ERK1/2 Signaling Contribute to the Role of Gfi1 in Granulopoiesis. Sci Rep 9(1):737 |
| abstractText | Gfi1 supports neutrophil development at the expense of monopoiesis, but the underlying molecular mechanism is incompletely understood. We recently showed that the G-CSFR Y729F mutant, in which tyrosine 729 was mutated to phenylalanine, promoted monocyte rather than neutrophil development in myeloid precursors, which was associated with prolonged activation of Erk1/2 and enhanced activation of c-Fos and Egr-1. We show here that Gfi1 inhibited the expression of c-Fos, Egr-1 and Egr-2, and rescued neutrophil development in cells expressing G-CSFR Y729F. Gfi1 directly bound to and repressed c-Fos and Egr-1, as has been shown for Egr-2, all of which are the immediate early genes (IEGs) of the Erk1/2 pathway. Interestingly, G-CSF- and M-CSF-stimulated activation of Erk1/2 was augmented in lineage-negative (Lin(-)) bone marrow (BM) cells from Gfi1(-/-) mice. Suppression of Erk1/2 signaling resulted in diminished expression of c-Fos, Egr-1 and Egr-2, and partially rescued the neutrophil development of Gfi1(-/-) BM cells, which are intrinsically defective for neutrophil development. Together, our data indicate that Gfi1 inhibits the expression of c-Fos, Egr-1 and Egr-2 through direct transcriptional repression and indirect inhibition of Erk1/2 signaling, and that Gfi1-mediated downregulation of c-Fos, Egr-1 and Egr-2 may contribute to the role of Gfi1 in granulopoiesis. |
