Complex transcriptional regulation of myc family gene expression in the developing mouse brain and liver.
Complex transcriptional regulation of myc family gene expression in the developing mouse brain and liver.
复制标题
发育中的小鼠大脑和肝脏中 myc 家族基因表达的复杂转录调控。
DOI：
10.1128/mcb.11.12.6007-6015.1991
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发表时间：
1991
影响因子：
5.3
通讯作者：
DePinho,RA
中科院分区：
文献类型：
--
作者：
Xu,L;Morgenbesser,SD;DePinho,RA
mycfamily基因（c-、N-和L-myc）已经显示出相对于组织类型和发育阶段的差异表达。为了定义和比较其差异发育表达的调控机制，我们研究了小鼠出生后大脑和肝脏发育过程中每个mycfamily成员的转录调控。核运行的转录测定表明，转录起始的速率和转录阻断的程度都以复杂的方式对所有三个基因的调节做出贡献。在出生后的大脑发育过程中，每个转录控制机制对myc家族基因表达的调节的相对贡献被发现对于每个基因是不同的。例如，虽然转录衰减的调节似乎没有导致L-mycmRNA表达的下调，但发现衰减是稳态N-mycmRNA水平下调的主要机制。不同的转录策略被发现在新生儿与成人发育中的肝脏中用于抑制N-和L-myc表达。新生儿肝脏中不可检测的稳态N-和L-mycmRNA水平与非常低的转录起始速率相关，而在成人阶段缺乏N-和L-mycmRNA表达伴随着高起始速率和显著的转录衰减程度。在N-mycgene的转录衰减被发现映射到一个区域编码一个潜在的茎环结构，然后由胸腺嘧啶道内的第一个外显子，并不依赖于使用一个特定的转录起始位点。
mycfamily genes (c-, N-, and L-myc)have been shown to be differentially expressed with respect to tissue type and developmental stage. To define and compare the regulatory mechanisms governing their differential developmental expression, we examined the transcriptional regulation of eachmycfamily member during murine postnatal brain and liver development. Nuclear run-on transcription assays demonstrated that both the rate of transcriptional initiation and the degree of transcriptional blocking contribute in a complex manner to the regulation of all three genes. During postnatal brain development, the relative contribution of each transcriptional control mechanism to the regulation ofmycfamily gene expression was found to be different for each gene. For instance, while modulation of transcriptional attenuation did not appear to contribute to the down-regulation of L-mycexpression, attenuation was found to be the dominant mechanism by which steady-state N-mycmRNA levels were down-regulated. Different transcriptional strategies were found to be employed in newborn versus adult developing liver for repression of N- and L-mycexpression. Undetectable steady-state N- and L-mycmRNA levels in newborn liver were associated with a very low rate of transcriptional initiation, whereas the lack of N- and L-mycexpression at the adult stage was accompanied by a high rate of initiation and a striking degree of transcriptional attenuation. Transcriptional attenuation in the N-mycgene was found to map to a region encoding a potential stem-loop structure followed by a thymine tract within the first exon and was not dependent on the use of a specific transcriptional start site.