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Blood, 15 March 2001, Vol. 97, No. 6, pp. 1861-1868
RED CELLS
Erythroid Kruppel-like factor (EKLF) coordinates erythroid cell
proliferation and hemoglobinization in cell lines derived from EKLF
null mice
Elise Coghill,
Sarah Eccleston,
Vanessa Fox,
Loretta Cerruti,
Clark Brown,
John Cunningham,
Stephen Jane, and
Andrew Perkins
From the Department of Physiology, Monash University,
and the Rotary Bone Marrow Research Laboratories, Royal Melbourne
Hospital and Melbourne University, Melbourne, Australia; and the
Department of Hematology/Oncology, St Jude Children's Research
Hospital, Memphis, TN.
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 -globin locus and then
reintroduced EKLF as a tamoxifen-inducible, EKLF-mutant estrogen
receptor (EKLF-ERTM) fusion protein. Addition of tamoxifen resulted in
enhanced differentiation and hemoglobinization, coupled with reduced
proliferation. Human -globin gene expression increased
significantly, whereas -globin transcripts remained elevated at
levels close to endogenous mouse -globin transcript levels. We
conclude that EKLF plays a role in regulation of the cell cycle and
hemoglobinization in addition to its role in -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.

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