GATA-1 dominantly activates a program of erythroid gene expression in factor-dependent myeloid FDCW2 cells.
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 betamaj-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.
Seshasayee
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Graduate Program in Genetics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Gaines
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Wojchowski
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DM
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D050981:Erythroid-Specific DNA-Binding Factors; D004920:Erythropoiesis / Q000235:genetics*; D004921:Erythropoietin / Q000378:metabolism; D016193:G1 Phase; D050982:GATA1 Transcription Factor; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007377:Interleukin-3 / Q000235:genetics; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D050783:Proto-Oncogene Proteins c-ets; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000502:physiology; D019089:Stem Cell Factor / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; C494042:Ets1 protein, mouse; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D007377:Interleukin-3; D051741:Kruppel-Like Transcription Factors; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D017467:Receptors, Erythropoietin; D019089:Stem Cell Factor; D014157:Transcription Factors; C080774:erythroid Kruppel-like factor; D004921:Erythropoietin; D005914:Globins