c-myc and c-fos gene regulation during mouse liver regeneration.
We have examined the expression of c-myc and c-fos proto-oncogenes in regenerating mouse liver, in order to analyse the relative contributions of transcriptional and post-transcriptional regulations in vivo. We show that c-myc and c-fos transcription is induced after partial hepatectomy, and involves common mechanisms. A strong block to transcriptional elongation exists in normal liver, within the first exon of c-myc gene. This block is only slightly relieved during liver regeneration, although transcriptional initiation is transiently increased (4-6 fold). In contrast, transcription initiation of c-fos is induced while the transcriptional block within the first exon of the gene is almost completely abolished. The steady-state levels of both transcripts increased to high levels (50-100 fold) within 2-6 h after partial hepatectomy, and were maintained for at least 40 h in the case of c-myc. We conclude that post-transcriptional control mechanisms are largely responsible for the dramatic induction of c-myc mRNA in regenerating liver, while c-fos mRNA accumulation is the result of both an increased initiation and a relief of a transcriptional block to elongation. Induction of both genes in vivo with cycloheximide argues in favor of negative trans-acting proteins which regulate initiation and elongation of transcription.
Sobczak
J
J
Laboratoire d'Enzymologie des Acides Nucléiques, URA 554 CNRS, Université Paris, VI, France.
Mechti
N
N
Tournier
M F
MF
Blanchard
J M
JM
Duguet
M
M
D000818:Animals; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D008099:Liver / Q000201:enzymology*; D008115:Liver Regeneration; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D015183:Restriction Mapping; D014158:Transcription, Genetic
D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D011505:Protein-Tyrosine Kinases