Contributions of transcriptional and post-transcriptional mechanisms to the regulation of c-myc expression in mouse erythroleukemia cells.
Contributions of transcriptional and post-transcriptional mechanisms to the regulation of c-myc expression in mouse erythroleukemia cells.
复制标题
转录和转录后机制对小鼠红白血病细胞 c-myc 表达调节的贡献。
DOI：
10.1101/gad.1.9.938
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发表时间：
1987
影响因子：
10.5
通讯作者：
Lachman,HM
中科院分区：
文献类型：
--
作者：
Nepveu,A;Marcu,KB;Skoultchi,AI;Lachman,HM
小鼠红白血病（MEL）细胞的化学诱导分化导致c-myc mRNA水平的复杂变化。添加诱导剂六亚甲基双乙酰胺（HMBA）后1-2小时内，c-myc mRNA水平下降10至20倍，并保持较低水平，直至1 - 2 -24小时，此时mRNA重新积聚至其原始水平。此后，随着细胞进行终末分化，c-myc mRNA再次下降到低水平。我们已经调查了这些变化的调节，通过测量c-myc基因转录和mRNA周转。我们发现，早期快速下降的c-myc mRNA是由于增加的块内的c-myc第一外显子转录延长。然后，在HMBA处理2小时后，有效的c-myc转录恢复到未诱导细胞中存在的水平，并在分化程序的其余部分中保持。这些结果表明，除了诱导剂处理后c-myc mRNA迅速下降外，所有后续的信息水平调节均通过转录后机制发生。c-myc mRNA周转的研究表明，一些转录后调节是核。
Chemically induced differentiation of mouse erythroleukemia (MEL) cells leads to complex changes in c-myc mRNA levels. Within 1-2 hr after the addition of the inducer hexamethylene bisacetamide (HMBA), c-myc mRNA levels decrease 10-to 20-fold and remain low until 12-24 hr, at which time the mRNA reaccumulates to its original level. Thereafter as the cells undergo terminal differentiation, c-myc mRNA again declines to a low level. We have investigated the regulation of these changes by measuring c-myc gene transcription and mRNA turnover. We find that the early rapid decline in c-myc mRNA is due to an increase in the block to elongation of transcription within the c-myc first exon. Effective c-myc transcription is then restored after 2 hr of HMBA treatment to the level present in uninduced cells and is maintained throughout the remainder of the differentiation program. These results demonstrate that, except for the rapid decline in c-myc mRNA immediately following inducer treatment, all subsequent regulation of message levels occurs through post-transcriptional mechanisms. Studies of c-myc mRNA turnover suggest that some post-transcriptional regulation is nuclear.