Comparison of the expression and function of the transcription factor PU.1 (Spi-1 proto-oncogene) between murine macrophages and B lymphocytes

I L Ross, T L Dunn, X Yue, S Roy, C J Barnett, D A Hume

Research output: Contribution to journalArticlepeer-review

Abstract

The expression of mRNA encoding the DNA-binding protein PU.1 (Spi-1) is restricted to B lymphocytes and macrophages. The role of PU.1 in tissue-specific transcriptional regulation in the two cell types was examined by co-transfection of a PU.1 expression plasmid with vectors containing B cell (IgH enhancer) or macrophage-specific (c-fms) transcription control elements. Cotransfection of the PU.1 expression plasmid in MOPC31C B cells trans-repressed the IgH enhancer but trans-activated the c-fms promoter. The latter was insufficient to overcome a block to transcription elongation that determines macrophage-specific c-fms gene expression. In the macrophage line RAW264, PU.1 had no effect on the c-fms promoter, but trans-repressed the activity of a c-fms reporter plasmid containing the transcription attenuator. The effects of PU.1 in both cell types were distinct from those of c-ets-2, a related factor, which trans-activated the c-fms promoter in both B cells and macrophages but also repressed the IgH enhancer. PU.1 was shown to be one of several nuclear proteins that bound a critical cis-acting element of the IgH enhancer, microB, but analysis of nuclear extracts of a wide range of B cell and macrophage lines demonstrated a strong correlation between macrophage phenotype and nuclear PU.1 expression. The data suggest that differences in nuclear PU.1 expression and function between macrophages and B cells may play a role in lineage divergence.
Original languageEnglish
Pages (from-to)121-32
Number of pages12
JournalOncogene
Volume9
Issue number1
Publication statusPublished - Jan 1994

Keywords

  • Animals
  • B-Lymphocytes
  • Base Sequence
  • Carrier Proteins
  • Cells, Cultured
  • DNA-Binding Proteins
  • Escherichia coli
  • Genes, fms
  • Macrophages
  • Mice
  • Molecular Sequence Data
  • Proto-Oncogene Protein c-ets-2
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Repressor Proteins
  • Retroviridae Proteins, Oncogenic
  • Trans-Activators
  • Transcription Factors
  • Transcription, Genetic
  • Transfection

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