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Early Growth Response Transcriptional Regulators Are Dispensable for Macrophage Differentiation¹

John H. Carter^* and Warren G. Tourtellotte^2,*,,

^* Department of Pathology, Division of Neuropathology, and Department of Neurology, Northwestern University, Chicago, IL 60611

Early growth response (Egr) proteins comprise a family of transcriptional regulators (Egr1–4) that modulate gene expression involved in the growth and differentiation of many cell types. In particular, Egr1 is widely believed to have an essential role in regulating monocyte/macrophage differentiation. However, Egr1-deficient mice have normal numbers of functional macrophages, an observation that has led to the hypothesis that other Egr proteins may compensate for Egr1 function in vivo. We examined whether other Egr transcription factors have a functionally redundant role in monocyte/macrophage differentiation. Egr1 and Egr3 expression was found to be induced in myeloid cells when they were differentiated into macrophages by treatment with M-CSF, whereas Egr2 was minimally induced and Egr4 was not detected. In either Egr1/Egr3 or Egr1/Egr2 double homozygous mutant mice, macrophage differentiation and function remained unimpaired. Additionally, the expression of molecules that broadly inhibit Egr function failed to block commitment to the monocytic lineage or inhibit the maturation of monocyte precursors. Finally, several hemopoietic growth factors were found to induce Egr gene expression, indicating that Egr gene expression is not cell lineage specific. Taken together, these results demonstrate that Egr transcription factors are neither essential for nor specific to monocyte/macrophage differentiation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported by National Institutes of Health Grants (NS046468 and NS040748) and a Howard Hughes Faculty Scholar Award (to W.G.T.). J.H.C. was supported by a predoctoral fellowship from the National Institutes of Health (CA009560) and the National Institutes of Health Medical Scientist Training Program (GM008152).

² Address correspondence and reprint requests to Dr. Warren G. Tourtellotte, Northwestern University, Department of Pathology, W127, 330 E. Chicago Avenue, Chicago, IL 60611. E-mail address: warren{at}northwestern.edu

³ Abbreviations used in this paper: Egr, early growth response; dnEgr, dominant negative; Erg, EGFP, enhanced GFP; ERE, Egr response element. IRES, internal ribosome entry site; MSCV, main stem cell virus; P/S, penicillin/streptomycin; WT, wild type.

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