Extinction of expression of the PU.1/Sfpi-1 putative oncogene encoding a B-cell- and macrophage-specific...

Several examples of extinction of cell type-specific gene expression have been observed following fusion of different cell types. Possible mechanisms of the extinction include loss of transcriptional activators and acquisition of repressor factors responsible for cell type-specific gene expression. In this study, we demonstrated the extinction of expression of the PU.1/Sfpi-1 putative oncogene encoding a B-cell- and macrophage-specific transcription factor when plasmacytoma cells are fused with embryonal carcinoma (EC) cells. The hybrid cells retained most chromosome complements from both parental lines including chromosome 2 on which the PU.1 gene is located. Therefore, extinction of PU.1 gene expression in the hybrids is not likely the result of chromosome segregation but rather due to a transacting negative factor(s) present in EC cells. On the contrary, expression of the PU.1 mRNA in plasmacytoma cells was not extinguished upon cell fusion with T-lymphoma cells, although the parental T-lymphoma cells did not express PU.1 transcripts. Hence, T-lymphoma cells seemed to be permissive to PU.1 gene expression, while EC cells were repressive. These results suggest that PU.1 gene expression which positively regulates some B cell- and macrophage-specific gene expression is a target of negative regulatory mechanisms during cell differentiation, and the regulatory mechanisms repressing PU.1 gene expression is different between EC cells and T-cells.