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 Blood, 1 October 2005, Vol. 106, No. 7, pp. 2566-2571.
Prepublished online as a Blood First Edition Paper on June 9, 2005; DOI 10.1182/blood-2005-02-0674.

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RED CELLS

KLF2 is essential for primitive erythropoiesis and regulates the human and murine embryonic {beta}-like globin genes in vivo

Priyadarshi Basu, Pamela E. Morris, Jack L. Haar, Maqsood A. Wani, Jerry B. Lingrel, Karin M. L. Gaensler, and Joyce A. Lloyd

From the Department of Human Genetics, Virginia Commonwealth University, Richmond, VA; the Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA; the Department of Molecular Genetics, Biochemistry, and Microbiology, College of Medicine, University of Cincinnati, Cincinnati, OH; and the Department of Medicine, University of California, San Francisco, CA.

The Krüppel-like factors (KLFs) are a family of C2/H2 zinc finger DNA-binding proteins that are important in controlling developmental programs. Erythroid Krüppel-like factor (EKLF or KLF1) positively regulates the {beta}-globin gene in definitive erythroid cells. KLF2 (LKLF) is closely related to EKLF and is expressed in erythroid cells. KLF2-/- mice die between embryonic day 12.5 (E12.5) and E14.5, because of severe intraembryonic hemorrhaging. They also display growth retardation and anemia. We investigated the expression of the {beta}-like globin genes in KLF2 knockout mice. Our results show that KLF2-/- mice have a significant reduction of murine embryonic Ey- and {beta}h1-globin but not {zeta}-globin gene expression in the E10.5 yolk sac, compared with wild-type mice. The expression of the adult {beta}maj- and {beta}min-globin genes is unaffected in the fetal livers of E12.5 embryos. In mice carrying the entire human globin locus, KLF2 also regulates the expression of the human embryonic {epsilon}-globin gene but not the adult {beta}-globin gene, suggesting that this developmental-stage-specific role is evolutionarily conserved. KLF2 also plays a role in the maturation and/or stability of erythroid cells in the yolk sac. KLF2-/- embryos have a significantly increased number of primitive erythroid cells undergoing apoptotic cell death. (Blood. 2005;106: 2566-2571)


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