The Zinc Finger Transcription Factor Egr-1 Potentiates Macrophage Differentiation of Hematopoietic Cells

Previously we have shown that the zinc finger transcription factor Egr-1 is essential for and restricts differentiation of hematopoietic cells along the macrophage lineage, raising the possibility that Egr-1 actually plays a deterministic role in governing the development of hematopoietic precursor cells along the monocytic lineage. To test this hypothesis, we have taken advantage of interleukin-3-dependent 32Dcl3 hematopoietic precursor cells which, in addition to undergoing granulocytic differentiation in response to granulocyte colony-stimulating factor, were found to be induced for limited proliferation, but not differentiation, by granulocyte-macrophage colony-stimulating factor. It was shown that ectopic expression of Egr-1 blocked granulocyte colony-stimulating factor-induced terminal granulocytic differentiation, consistent with previous findings. In addition, ectopic expression of Egr-1 endowed 32Dcl3 cells with ability to be induced by granulocyte-macrophage colony-stimulating factor for terminal differentiation exclusively along the macrophage lineage. Thus, evidence that Egr-1 potentiates terminal macrophage differentiation has been obtained, suggesting that Egr-1 plays a deterministic role in governing the development of hematopoietic cells along the macrophage lineage.