TRANSCRIPTION FACTOR ERYTHROID KRUPPEL-LIKE FACTOR (ELKF) IS ESSENTIAL FOR THE ERYTHROPOIETIN-INDUCED HEMOGLOBIN PRODUCTION BUT NOT FOR PROLIFERATION, VIABILITY, OR MORPHOLOGICAL MATURATION

The erythroid Kruppel-like factor (EKLF) is essential for the transcri ption of beta(maj) globin in erythroid cells. We show here that RNA fo r this transcription factor did not alter during erythropoietin-induce d differentiation of J2E cells; however, EKLF protein content decrease d and was inversely related to globin production. This unexpected resu lt was also observed during chemically induced maturation of two murin e erythroleukemia cell lines. To explore the role of EKLF in erythroid terminal differentiation, an antisense EKLF construct was introduced into J2E cells. As a consequence EKLF RNA and protein levels fell by a pproximately 80%, and the cells were unable to manufacture hemoglobin in response to erythropoietin, The failure to produce hemoglobin was d ue to reduced transcription of not only globin genes but also key heme enzyme genes. However, numerous other genes, including several erythr oid transcription factors, were unaffected by the decrease in EKLF. Al though hemoglobin synthesis was severely impaired with depleted EKLF l evels, morphological maturation in response to erythropoietin continue d normally. Moreover, erythropoietin-induced proliferation and viabili ty were unaffected by the decrease in EKLF levels. We conclude that EK LF affects a specific set of genes, which regulates hemoglobin product ion and has no obvious effect on morphological changes, cell division, or viability in response to erythropoietin.