Erythroid overexpression of C/EBPgamma in transgenic mice affects gamma-globin expression and fetal liver erythropoiesis.
The CCAAT boxes of the beta-like globin genes interact with three proteins: NF-Y, GATA-1 and NFE-6. We demonstrate that NFE-6 contains C/EBPgamma, and address its role in globin gene regulation by erythroid overexpression of C/EBPgamma, and a dominant-negative form C/EBPgammaDeltaB, in mice. Elevated levels of C/EBPgamma, but not C/EBPgammaDeltaB, increase expression of the (fetal) gamma-globin relative to the (adult) beta-globin gene. Interestingly, fetal liver erythropoiesis is ablated when the C/EBPgamma and C/EBPgammaDeltaB levels are further increased in homozygous transgenics. We suggest that targeted expression of dominant-negative leucine zipper proteins is a generally applicable approach to ablate specific tissues in mice.
Zafarana
G
G
Erasmus University Rotterdam, MGC-Department of Cell Biology, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
Rottier
R
R
Grosveld
F
F
Philipsen
S
S
D000818:Animals; D001483:Base Sequence; D023081:CCAAT-Binding Factor / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D050981:Erythroid-Specific DNA-Binding Factors; D004920:Erythropoiesis / Q000235:genetics*; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D050982:GATA1 Transcription Factor; D018507:Gene Expression Regulation, Developmental; D005914:Globins / Q000235:genetics*; D016350:Leucine Zippers / Q000235:genetics; D008099:Liver / Q000196:embryology; D051379:Mice; D008822:Mice, Transgenic; D005810:Multigene Family; D014157:Transcription Factors / Q000235:genetics
D023081:CCAAT-Binding Factor; D022762:CCAAT-Enhancer-Binding Proteins; C405462:CCAAT-enhancer-binding protein-gamma; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D014157:Transcription Factors; D005914:Globins