Journal
BLOOD
Volume 106, Issue 7, Pages 2566-2571Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2005-02-0674
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Funding
- NHLBI NIH HHS [HL60080] Funding Source: Medline
- NIDDK NIH HHS [DK62154, R01 DK074694] Funding Source: Medline
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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 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.
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