Global transcriptional regulation of the locus encoding the skeletal muscle determination genes Mrf4 and Myf5
Global transcriptional regulation of the locus encoding the skeletal muscle determination genes Mrf4 and Myf5
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DOI：
10.1101/gad.442408
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发表时间：
2008-01-15
影响因子：
10.5
通讯作者：
Rigby, Peter W. J.
中科院分区：
文献类型：
--
作者：
Carvajal, Jaime J.;Keith, Annette;Rigby, Peter W. J.
连锁的Mrf 4和Myf 5基因编码两个转录因子，这两个转录因子对于胚胎中骨骼肌的确定和分化至关重要。该基因座由大量交叉指状增强子控制，这些增强子在不同时间和精确定义的祖细胞群中激活基因表达。操纵基因座的增强子-启动子组合物揭示了调节这种基因簇的新机制。增强子、启动子和一类我们称之为转录平衡序列的新元件，它们可以作为隐蔽启动子，存在于一系列平衡中，以确保增强子和启动子一起产生两个基因的高度动态和精确特异的表达模式。所提出的模型依赖于增强子和最小的和隐藏的启动子之间的非生产性相互作用，并且不同于针对β-珠蛋白和Hox簇开发的那些。此外，它提供了一个解释的三个Mrf 4敲除等位基因的意想不到的表型。
The linked Mrf4 and Myf5 genes encode two transcription factors essential for the determination and differentiation of skeletal muscle in the embryo. The locus is controlled by a multitude of interdigitated enhancers that activate gene expression at different times and in precisely defined progenitor cell populations. Manipulation of the enhancer-promoter composition of the locus reveals a novel mechanism for the regulation of such a gene cluster. Enhancers, promoters, and a new class of elements we call transcription balancing sequences, which can act as cryptic promoters, exist in a series of equilibria to ensure that enhancers and promoters together produce the highly dynamic and exquisitely specific expression patterns of the two genes. The proposed model depends upon nonproductive interactions between enhancers and both minimal and cryptic promoters, and is distinct from those developed for the beta-globin and Hox clusters. Moreover, it provides an explanation for the unexpected phenotypes of the three Mrf4 knockout alleles.