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Mol Cell Biol, June 1998, p. 3278-3288, Vol. 18, No. 6
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

GATA-1 Dominantly Activates a Program of Erythroid Gene Expression in Factor-Dependent Myeloid FDCW2 Cells

Dhaya Seshasayee,1,2,3 Peter Gaines,2,3 and Don M. Wojchowski1,2,3,*

Graduate Program in Genetics,1 Center for Gene Regulation,2 and Department of Veterinary Science,3 The Pennsylvania State University, University Park, Pennsylvania 16802

Received 21 November 1997/Returned for modification 16 January 1998/Accepted 9 March 1998

Erythrocyte development has previously been shown to depend upon the expression of the lineage-restricted trans-acting factor GATA-1. Despite predicted roles for this factor during early development, GATA-1-deficient cells in chimeric mice and embryonic stem cell cultures mature to a late proerythroblast stage and express at least certain genes that normally are thought to be regulated by GATA-1 (including erythroid Krüppel-like factor [EKLF] and the erythropoietin [Epo] receptor). Opportunities to test roles for GATA-1 in erythroid gene activation in these systems therefore are limited. In the present study, in an alternate approach to test the function of GATA-1, GATA-1 has been expressed together with the Epo receptor in myeloid FDCW2 cells and the resulting effects on cytokine-dependent proliferation and erythroid gene expression have been assessed. GATA-1 expression at low levels delayed FDCW2ER cell cycle progression at the G1 phase specifically during Epo-induced mitogenesis. Upon expression of GATA-1 at increased levels, proliferation in response to Epo, interleukin-3 (IL-3), and stem cell factor was attenuated and endogenous GATA-1, EKLF and beta maj-globin gene expression was activated. Friend of GATA-1 (FOG) transcript levels also were enhanced, and ets-1 and c-mpl but not Epo receptor gene expression was induced. Finally, in FDCW2 cells expressing increased levels of GATA-1 and a carboxyl-terminally truncated Epo receptor, Epo (with respect to IL-3 as a control) was shown to markedly promote globin transcript expression. Thus, novel evidence for select hierarchical roles for GATA-1 and Epo in erythroid lineage specification is provided.

* Corresponding author. Mailing address: 115 William L. Henning Building, The Pennsylvania State University, University Park, PA 16802. Phone: (814) 865-0657. Fax: (814) 863-6140. E-mail: DMW1{at}psu.edu.

Mol Cell Biol, June 1998, p. 3278-3288, Vol. 18, No. 6
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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