MYB AND NF-M - COMBINATORIAL ACTIVATORS OF MYELOID GENES IN HETEROLOGOUS CELL-TYPES

The c-Myb transcription factor regulates the differentiation of immatu re erythroid, lymphoid, and myeloid cells, although only the latter ce lls become transformed by the v-myb oncogene. These are also the only cells that express the Myb-regulated gene mim-1, suggesting that Myb r equires tissue-specific, cooperating factors to activate such genes. H ere, we investigated the tissue-specific regulation of the mim-1 promo ter and found that it not only contains binding sites for Myb but also for NF-M, a myeloid-specific transcription factor that probably corre sponds to mammalian C/EBPbeta. Both types of binding sites were found to be required for full activity of the promoter. Remarkably, ectopic coexpression of Myb and NF-M proteins in erythroid cells or fibroblast s was sufficient to induce endogenous markers of myeloid differentiati on, like the mim-1 and lysozyme genes. Our results indicate that c-Myb and NF-M proteins act as a bipartite, combinatorial signal that regul ates the expression of myeloid-specific genes, even in heterologous ce ll types.