Opposing Actions of c-ets/PU.1 and c-myb Protooncogene Products in Regulating the Macrophage-specific Promoters of the Human and Mouse Colony-stimulating Factor-1 Receptor (c-fins) Genes

The receptor for macropbage colony stimulating factor (CSF-1), the c-f ms gene product, is a key determinant in the differentiation of monocytic phagocytes. Dissection of the human and mouse c-frns proximal promoters revealed opposing roles for nuclear protooncogenes in the transcriptional regulation of this gene. On the one hand, c-ets-I, c-ets-2, and the macrophagespecific factor PU.1, but not the ets-factor PEA3, trans-activated the c-f ms proximal promoter. On the other hand c-myb repressed proximal promoter activity in macrophages and blocked the action of c-ets-1 and c-ets-2. Basal c-f ms promoter activity was almost undetectable in the M1 leukaemia line, which expressed high levels of c-myb, but was activated as cells differentiated in response to leukemia inhibitory factor and expressed c-f ms mRNA. The repressor function of c-myb depended on the COOH-terminal domain of the protein. We propose that ets-factors are necessary for the tissue-restricted expression of c-f ms and that c-myb acts to ensure correct temporal expression of c-f ms during myeloid differentiation.