KLF2 is essential for primitive erythropoiesis and regulates the human and murine embryonic beta-like globin genes in vivo.
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.
Basu
Priyadarshi
P
Department of Human Genetics, Virginia Commonwealth University, PO Box 980033, Richmond, VA 23298-0033, USA.
Morris
Pamela E
PE
Haar
Jack L
JL
Wani
Maqsood A
MA
Lingrel
Jerry B
JB
Gaensler
Karin M L
KM
Lloyd
Joyce A
JA
D000818:Animals; D017209:Apoptosis; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000648:ultrastructure; D004920:Erythropoiesis; D005260:Female; D005786:Gene Expression Regulation; D005914:Globins / Q000096:biosynthesis*; D006801:Humans; D020287:In Situ Nick-End Labeling; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D017931:DNA Primers; D004268:DNA-Binding Proteins; C096161:KLF2 protein, human; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; C080774:erythroid Kruppel-like factor; D005914:Globins