Independent regulation of transcription of the two strands of the c-myc gene.

Previously we demonstrated the existence of transcripts from the noncoding strand of a rearranged, truncated c-myc gene in murine plasmacytomas in which this oncogene is translocated to an immunoglobulin constant-region gene element (M. Dean, R. B. Kent, and G. E. Sonenshein, Nature [London] 305:443-446, 1983). Here we report on the transcription of the two strands of a normal, unrearranged c-myc gene. We examined the effects of gene rearrangements, growth state transitions, and differentiation on the relative levels of usage of the two strands. Transcription from intron 1 to exon 3 of the murine c-myc gene was studied in in vitro nuclear runoff assays. The level of transcription of the noncoding strand across this region of a germ line c-myc gene in a murine B-cell lymphoma line was comparable to the level observed in plasmacytomas with translocated c-myc genes. Rapid changes in transcription of the coding strand of the c-myc gene could be seen during growth arrest of WEHI 231 cells and during activation of splenic T lymphocytes. Transcription of the noncoding strand was constitutive during these growth state transitions and during activation of primary cultures of quiescent calf aortic smooth muscle cells as well. In contrast, differentiation of murine erythroleukemia cells was accompanied by an early drop in transcription of the two strands of this gene. The ramifications of these findings with respect to measurements of c-myc gene transcription and to the regulation of this gene are discussed.