[Repression of rearranged c-myc expression in murine cell hybrids]

In hybrids SBW I and SBW II between S194 mouse plasmacytoma and BW5147 mouse T-cell lymphoma, enhanced expression of the rearranged c-myc mRNA of heterogeneous sizes (1.8-2.4 kb) in S194 was markedly downregulated but expression of the non-rearranged c-myc of 2.4 kb in BW5147 was not. Treatment of SBW I hybrid cells with cycloheximide augmented non-rearranged c-myc expression 2-4-fold but did not release the downregulated expression of the rearranged c-myc. Nuclear run-on assay showed that the high level of c-myc transcripts in S194 cells declined in SBW I cells comparable to the level in BW5147 cells. The results suggest that the downregulation of the rearranged c-myc in SBW I hybrid cells was at a transcriptional level rather than a posttranscriptional level. Methylation patterns of the rearranged c-myc in SBW I cells was the same as S194 cells. Treatment of the SBW I cells with 5-azacytidine, TPA or forskolin did not release the downregulated expression of the rearranged c-myc, suggesting no causative involvement of DNA methylation or protein phosphorylation in the downregulation. Higher DNase I sensitivity of the rearranged c-myc in S194 cells decreased to a similar extent to that of the non-rearranged c-myc after cell fusion with BW5147 cells. All these results suggest that expression of the rearranged c-myc was downregulated at the level of transcription in murine cell hybrids between a plasmacytoma and a T-cell lymphoma probably by changing the chromatin configuration around the gene from the open to the closed state.