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-fms) genes.
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.
Department of Microbiology, Duke University Medical Center, Durham, North Carolina 27710.
M A
MA
Reddy
B S
BS
Yang
X
X
Yue
C J
CJ
Barnett
I L
IL
Ross
M J
MJ
Sweet
D A
DA
Hume
M C
MC
Ostrowski
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D002522:Chlorocebus aethiops; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D016236:Genes, fms; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D020598:Proto-Oncogene Proteins c-myb; D011519:Proto-Oncogenes; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D020598:Proto-Oncogene Proteins c-myb; D011994:Recombinant Proteins; D014157:Transcription Factors; D016186:Receptor, Macrophage Colony-Stimulating Factor