Mode of c-myc gene regulation in folic acid-induced kidney regeneration.

We have examined the contributions of transcriptional and post-transcriptional control mechanisms for the regulated activation of the c-myc proto-oncogene in regenerating kidney tissue in vivo. The c-myc gene is activated in kidney tubule cells which are induced to proliferate as a consequence of folic acid-induced renal injury in vivo. We show that c-myc transcriptional initiation is induced in a co-ordinate fashion with a strong block to transcriptional elongation within the gene's first exon. Therefore, transcription is not effectively induced throughout the c-myc gene in these regenerating renal cells. In contrast, initiation of c-fos gene transcription was induced while the degree of transcriptional blockage within the gene's first exon remained constant. The steady-state levels of myc transcripts, originating from the gene's P1 and P2 start sites, accumulated to very high levels within 4-6 hr which were maintained for at least 24 hr after folic acid treatment. We conclude that post-transcriptional control mechanisms are largely responsible for the dramatic induction of c-myc mRNAs in regenerating kidney tissue in vivo.