C-MAF INTERACTS WITH C-MYB TO REGULATE TRANSCRIPTION OF AN EARLY MYELOID GENE DURING DIFFERENTIATION

The MafB transcriptional activator plays a pivotal role in regulating lineage-specific gene expression during hematopoiesis by repressing Et s-1-mediated transcription of key erythroid-specific genes in myeloid cells. To determine the effects of Maf family proteins on the transact ivation of myeloid specific genes in myeloid cells, we tested the abil ity of c-Maf to influence Ets-1- and c-Myb-dependent CD13/APN transcri ption. Expression of c-Maf in human immature myeloblastic cells inhibi ted CD13/APN-driven reporter gene activity (85 to 95% reduction) and r equired the binding of both c-Myb and Ets, but not Maf, to the promote r fragment. c-Mafs inhibition of CD13/APN expression correlates with i ts ability to physically associate with c-Myb. While c-Maf mRNA and pr otein levels remain constant during myeloid differentiation, formation of inhibitory Myb-Maf complexes was developmentally regulated, with t heir levels being highest in immature myeloid cell lines and markedly decreased in cell lines representing later developmental stages. This pattern matched that of CD13/APN reporter gene expression, indicating that Maf modulation of c-Myb activity may be an important mechanism fo r the control of gene transcription during hematopoietic cell developm ent.