Erythroid Kruppel-like factor (EKLF) coordinates erythroid cell proliferation and hemoglobinization in cell lines derived from EKLF null mice

Erythroid Kruppel-like factor (EKLF) is a transcription factor of the C2H2 zinc-finger class that is essential for definitive erythropoiesis. We gener ated immortal erythroid cell lines from EKLF-/- fetal liver progenitor cell s that harbor a single copy of the entire human beta -globin locus and then reintroduced EKLF as a tamoxifen-inducible, EKLF-mutant estrogen receptor (EKLF-ER(TM)) fusion protein. Addition of tamoxifen resulted in enhanced di fferentiation and hemoglobinization, coupled with reduced proliferation. Hu man beta -globin gene expression increased significantly, whereas gamma -gl obin transcripts remained elevated at levels close to endogenous mouse alph a -globin transcript levels. We conclude that EKLF plays a role in regulati on of the cell cycle and hemoglobinization in addition to its role in beta -globin gene expression. The cell lines we used will facilitate structural and functional analyses of EKLF in these processes and provide useful tools for the elucidation of nonglobin EKLF target genes.(Blood. 2001;97:1861-18 68) (C) 2001 by The American Society of Hematology.