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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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Submitted February 17, 2005
Accepted May 26, 2005

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 Gaensler, and Joyce A Lloyd*

Department of Human Genetics, Virginia Commonwealth University, Richmond, Virginia, USA
Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, Virginia, USA
Department of Molecular Genetics, Biochemistry, and Microbiology, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA
Department of Medicine, University of California, San Francisco, California, USA

* Corresponding author; email: jlloyd{at}hsc.vcu.edu.

The Kruppel-like factors (KLFs) are a family of C2/H2 zinc finger DNA binding proteins that are important in controlling developmental programs. Erythroid Kruppel-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 E12.5 and E14.5, due to severe intra-embryonic 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 to 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.


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