Erythroid overexpression of C/EBPγ in transgenic mice affects γ-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/EBP gamma, and address its role in globin gene regulation by erythroid overexpression of C/EBP gamma, and a dominant-negative form C/EBP gamma DeltaB, in mice. Elevated levels of C/EBP gamma, but not C/EBP gamma DeltaB, increase expression of the (fetal) gamma -globin relative to the (adult) beta -globin gene. Interestingly, fetal liver erythropoiesis is ablated when the C/EBP gamma and C/EP gamma DeltaB 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.