Erythroid Kruppel-like factor (EKLF) is a transcription factor of the C2H2 zinc-finger class that is essential for definitive erythropoiesis. We generated immortal erythroid cell lines from EKLF−/− fetal liver progenitor cells that harbor a single copy of the entire human β-globin locus and then reintroduced EKLF as a tamoxifen-inducible, EKLF–mutant estrogen receptor (EKLF-ER™) fusion protein. Addition of tamoxifen resulted in enhanced differentiation and hemoglobinization, coupled with reduced proliferation. Human β-globin gene expression increased significantly, whereas γ-globin transcripts remained elevated at levels close to endogenous mouse α-globin transcript levels. We conclude that EKLF plays a role in regulation of the cell cycle and hemoglobinization in addition to its role in β-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.

  • Submitted January 10, 2000.
  • Accepted October 26, 2000.
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