Abstract
Regulation of the rearranged and non‐rearranged c‐myc expression was studied in murine cell hybrids (SBWI and SBWII) between plasmacytoma (S194) and T‐cell lymphoma (BWS147) cells. Expression of the rearranged c‐myc of heterogeneous mRNA sizes (1.8 ∼ 2.4 kb) was markedly down‐regulated in these hybrids regardiess of retention of the gene. On the other hand, expression of the non‐rearranged c‐myc (2.4 kb) was not significantly affected in these hybrids. Treatment of SBWI hybrid ceiis with cycloheximide enhanced the non‐rearranged c‐myc 2‐ to 4‐fold but did not release the down‐regulation of the rearranged c‐myc at all, suggesting that the down‐regulation of the rearranged c‐myc in the hybrid cells was mainly at a transcriptional rather than a post‐transcriptional level. This was supported by the results of nuclear run‐on assay: the high level of run‐on transcripts in S194 cells declined in SBWI hybrid cells comparable to the level in BW5147 cells. The rearranged c‐myc was hemi‐methylated in S194 cells and the pattern was the same in SBWI hybrid cells. Furthermore, down‐regulation of the rearranged c‐myc in the hybrid was also not restored by treatment with 5‐azacytidine (5‐AzaC), 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) or forskolin, suggesting no causative involvement of DNA methylation or protein phosphorylation in down‐regulation. 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. These results suggest that expression of the rearranged c‐myc is down‐regulated at the level of transcription in murine cell hybrids between a plasmacytoma and a T‐cell lymphoma, probably by changing chromatin configuration around the gene from the open to the closed state.