c-myc and c-fos gene regulation during mouse liver regeneration.

c-myc and c-fos gene regulation during mouse liver regeneration.
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发表时间:
1989-12
期刊:
影响因子:
8
通讯作者:
J. Sobczak;N. Mechti;M. Tournier;J. Blanchard;M. Duguet
J. Sobczak;N. Mechti;M. Tournier;J. Blanchard;M. Duguet
中科院分区:
医学1区
文献类型:
--
作者:
J. Sobczak;N. Mechti;M. Tournier;J. Blanchard;M. Duguet

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我们研究了c-myc和c-fos原癌基因在再生小鼠肝脏中的表达,以分析体内转录和转录后调控的相对贡献。我们发现,c-myc和c-fos转录诱导后部分肝切除术,并涉及共同的机制。在正常肝脏中,c-myc基因的第一个外显子内存在对转录延伸的强阻断。这种阻断在肝再生过程中仅轻微缓解,尽管转录起始瞬时增加(4-6倍)。相反,c-fos的转录起始被诱导,而基因的第一外显子内的转录阻断几乎完全被废除。两种转录物的稳态水平在部分肝切除术后2-6小时内增加到高水平(50-100倍),并且在c-myc的情况下维持至少40小时。我们的结论是,转录后控制机制主要是负责显着诱导c-myc mRNA在再生肝脏,而c-fos mRNA的积累是一个增加的启动和救济的转录块延长的结果。放线菌酮在体内诱导这两个基因主张有利于负反式作用蛋白质,调节转录的起始和延伸。
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.