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.
|Keywords||Animals, Base Sequence, CCAAT-Binding Factor/genetics, CCAAT-Enhancer-Binding Proteins/*genetics, DNA Primers/genetics, DNA-Binding Proteins/genetics, Erythroid-Specific DNA-Binding Factors, Erythropoiesis/*genetics, Fetal Blood/cytology/metabolism, GATA1 Transcription Factor, Gene Expression Regulation, Developmental, Globins/*genetics, Leucine Zippers/genetics, Liver/embryology, Mice, Mice, Transgenic, Multigene Family, Research Support, Non-U.S. Gov't, Transcription Factors/genetics|
|Persistent URL||dx.doi.org/10.1093/emboj/19.21.5856, hdl.handle.net/1765/12904|
Zafarana, G., Rottier, R.R., Grosveld, F.G., & Philipsen, S.. (2000). Erythroid overexpression of C/EBPgamma in transgenic mice affects gamma-globin expression and fetal liver erythropoiesis.. EMBO Journal, 19(21), 5856–5863. doi:10.1093/emboj/19.21.5856