Abstract
The receptor for macrophage colony stimulating factor (CSF-1), the c-fms gene product, is a key determinant in the differentiation of monocytic phagocytes. Dissection of the human and mouse c-fms proximal promoters revealed opposing roles for nuclear protooncogenes in the transcriptional regulation of this gene. On the one hand, c-ets-1, c-ets-2, and the macrophage-specific factor PU.1, but not the ets-factor PEA3, trans-activated the c-fms 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-fms 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-fms 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-fms and that c-myb acts to ensure correct temporal expression of c-fms during myeloid differentiation.
Original language | English |
---|---|
Pages (from-to) | 2309-19 |
Number of pages | 11 |
Journal | Journal of Experimental Medicine |
Volume | 180 |
Issue number | 6 |
Publication status | Published - 1 Dec 1994 |
Keywords / Materials (for Non-textual outputs)
- 3T3 Cells
- Animals
- Base Sequence
- Cell Differentiation
- Cell Line
- Cercopithecus aethiops
- DNA Primers
- DNA-Binding Proteins
- Gene Expression Regulation
- Genes, fms
- Humans
- Mice
- Molecular Sequence Data
- Oncogenes
- Polymerase Chain Reaction
- Promoter Regions, Genetic
- Proto-Oncogene Proteins
- Proto-Oncogene Proteins c-ets
- Proto-Oncogene Proteins c-myb
- Proto-Oncogenes
- Receptor, Macrophage Colony-Stimulating Factor
- Recombinant Proteins
- Transcription Factors
- Tumor Cells, Cultured