A MyoD-generated feed-forward circuit temporally patterns gene expression during skeletal muscle differentiation
A MyoD-generated feed-forward circuit temporally patterns gene expression during skeletal muscle differentiation
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DOI：
10.1101/gad.1234304
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发表时间：
2004-10-01
影响因子：
10.5
通讯作者：
Tapscott, SJ
中科院分区：
文献类型：
--
作者：
Penn, BH;Bergstrom, DA;Tapscott, SJ
不同细胞类型的发育和分化是通过基因子集的顺序表达实现的;然而，在时间上模式化基因表达的分子机制在很大程度上仍然未知。在骨骼肌发生中，基因表达由MyoD启动，包括特异性Mef 2亚型的表达和p38丝裂原活化蛋白激酶（MAPK）途径的激活。在这里，我们表明，p38活性促进MyoD和Mef 2结合在一个子集的后期激活的启动子，和Mef 2D的结合招聘Pol II。最重要的是，通过p38的早熟激活和Mef 2D的表达，晚期激活基因的表达可以转移到分化的早期阶段，这表明MyoD介导的前馈回路在时间上对基因表达进行模式化。
The development and differentiation of distinct cell types is achieved through the sequential expression of subsets of genes; yet, the molecular mechanisms that temporally pattern gene expression remain largely unknown. In skeletal myogenesis, gene expression is initiated by MyoD and includes the expression of specific Mef2 isoforms and activation of the p38 mitogen-activated protein kinase (MAPK) pathway. Here, we show that p38 activity facilitates MyoD and Mef2 binding at a subset of late-activated promoters, and the binding of Mef2D recruits Pol II. Most importantly, expression of late-activated genes can be shifted to the early stages of differentiation by precocious activation of p38 and expression of Mef2D, demonstrating that a MyoD-mediated feed-forward circuit temporally patterns gene expression.