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

M A Reddy, B S Yang, X Yue, C J Barnett, I L Ross, M J Sweet, D A Hume, M C Ostrowski

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)2309-19
Number of pages11
JournalJournal of Experimental Medicine
Volume180
Issue number6
Publication statusPublished - 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

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