The first exon of the c-myc proto-oncogene contains a novel positive control element

We have identified a positive modulator within the c-myc first exon downstream of the gene's transcription initiation sites, P1 and P2. We introduced myc-CAT (chloramphenicol acetyltransferase) hybrid genes into three cell lines (BJAB, COS and HeLa) and measured their expression by either CAT enzymatic activity, S1 nuclease protection or by a nuclear 'run-on' transcription assay. Removal of 46 bp from the 3' end of the first exon results in a decrease of myc-CAT expression and P2 activity. A 438-bp exon 1 segment, lacking the normal myc promoters, efficiently drives the expression of SV40 early promoters. We find that this first exon segment efficiently functions as a positive modulator only in its sense orientation, 3' of a nearby promoter. The positive effects of the myc first exon and the SV40 enhancer are complementary.