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.
Asselin
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Biochemistry Department, SUNY, Stony Brook 11794-5215.
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D000818:Animals; D005492:Folic Acid / Q000494:pharmacology; D007668:Kidney / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D012313:RNA / Q000032:analysis; D012038:Regeneration; D014158:Transcription, Genetic
D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012313:RNA; D005492:Folic Acid