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在中枢神经系统中,成肌决定基因Myf5转录异常背后的调控机制。

The regulatory mechanisms that underlie inappropriate transcription of the myogenic determination gene Myf5 in the central nervous system.

作者信息

Daubas Philippe, Crist Colin G, Bajard Lola, Relaix Frédéric, Pecnard Emmanuel, Rocancourt Didier, Buckingham Margaret

机构信息

Institut Pasteur, CNRS URA 2578, Department of Developmental Biology, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.

出版信息

Dev Biol. 2009 Mar 1;327(1):71-82. doi: 10.1016/j.ydbio.2008.11.031. Epub 2008 Dec 7.

DOI:10.1016/j.ydbio.2008.11.031
PMID:19100730
Abstract

Myf5 is a key myogenic determination factor, specifically present at sites of myogenesis. Surprisingly, during mouse development, this gene is also transcribed in restricted areas of the central nervous system, although the Myf5 protein is not detectable. We have investigated the regulation of Myf5 expression in the central nervous system. Using both in ovo electroporation in the chick embryo and transgenesis in the mouse, we show that regulatory sequences that direct neuronal Myf5 transcription are present in a distal element located between -55 and -54.3 Kb from the Myf5 gene. An Oct6/Tst1 binding site is required for embryonic brain expression, and in the Oct6 mutant mouse embryo, Myf5 transcripts are no longer detectable in the brain. The Wnt-beta catenin signalling pathway is also implicated. Finally we show that post-transcriptional regulation of Myf5 gene expression involves miRNA repression acting through the Myf5-3'UTR.

摘要

Myf5是一个关键的成肌决定因子,特别存在于肌生成部位。令人惊讶的是,在小鼠发育过程中,尽管检测不到Myf5蛋白,但该基因也在中枢神经系统的特定区域转录。我们研究了中枢神经系统中Myf5表达的调控。通过在鸡胚中进行卵内电穿孔和在小鼠中进行转基因,我们发现指导神经元Myf5转录的调控序列存在于Myf5基因上游-55至-54.3 kb之间的一个远端元件中。一个Oct6/Tst1结合位点是胚胎脑表达所必需的,在Oct6突变小鼠胚胎中,脑中不再能检测到Myf5转录本。Wnt-β连环蛋白信号通路也与之相关。最后我们表明,Myf5基因表达的转录后调控涉及通过Myf5 3'非翻译区起作用的miRNA抑制。

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