Erythroid overexpression of C/EBP gamma 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/EBP gamma, a nd address its role in globin gene regulation by erythroid overexpression o f C/EBP gamma, and a dominant-negative form C/EBP gamma DeltaB, in mice. El evated levels of C/EBP gamma, but not C/EBP gamma DeltaB, increase expressi on of the (fetal) gamma -globin relative to the (adult) beta -globin gene. Interestingly, fetal liver erythropoiesis is ablated when the C/EBP gamma a nd C/EP gamma DeltaB levels are further increased in homozygous transgenics . We suggest that targeted expression of dominant-negative leucine zipper p roteins is a generally applicable approach to ablate specific tissues in mi ce.