MafB represses erythroid genes and differentiation through direct interaction with c-Ets-1.

Using a yeast interaction screen with a DNA-bound Ets-1 protein we have identified MafB as a direct interaction partner. This distant AP-1 relative, which is specifically expressed in myelomonocytic cells, binds to the DNA binding domain of Ets-1 via its basic region/leucine zipper domain. MafB represses Ets-1 transactivation of synthetic promoters containing Ets binding sites in yeast as well as avian cells. Both Ets-1 and Maf family proteins have been implicated in erythroid specific gene expression. Here we show that MafB inhibits Ets-1-mediated transactivation of the transferrin receptor, which is essential for heme synthesis and erythroid differentiation. Consequently, overexpression of MafB in an erythroblast cell line down-regulates the endogenous transferrin receptor gene and inhibits the cells' potential to differentiate into erythrocytes, without affecting cellular proliferation.