MAFB IS AN INTERACTION PARTNER AND REPRESSOR OF ETS-1 THAT INHIBITS ERYTHROID-DIFFERENTIATION

Using a yeast one-hybrid screen with a DNA-bound Ets-1 protein, we hav e identified MafB, an AP-1 like protein, as a direct interaction partn er. MafB is specifically expressed in myelomonocytic cells and binds t o the DNA-binding domain of Ets-1 via its basic region or leucine-zipp er domain. Furthermore, it represses Ets-1 transactivation of syntheti c promoters containing Ets binding sites and inhibits Ets-1-mediated t ransactivation of the transferrin receptor, which is known to be essen tial for erythroid differentiation, Accordingly, overexpression of Maf B in an erythroblast cell line down-regulates the endogenous transferr in receptor gene and inhibits differentiation without affecting cell p roliferation. These results highlight the importance of inhibitory int eractions between transcription factors in regulating lineage-specific gene expression.