Comparison of the expression and function of the transcription factor PU.1 (Spi-1 proto-oncogene) between murine macrophages and B lymphocytes.
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.
Ross
I L
IL
Centre for Molecular Biology and Biotechnology, University of Queensland, Australia.
Dunn
T L
TL
Yue
X
X
Roy
S
S
Barnett
C J
CJ
Hume
D A
DA
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D002352:Carrier Proteins / Q000032:analysis; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D016236:Genes, fms; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins; D015682:Retroviridae Proteins, Oncogenic; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C107465:ERF protein, human; C494070:Ets2 protein, mouse; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D015682:Retroviridae Proteins, Oncogenic; D015534:Trans-Activators; D014157:Transcription Factors; C062022:v-Spi-1 protein, Friend spleen focus-forming virus