CTCF Promotes Muscle Differentiation by Modulating the Activity of Myogenic Regulatory Factors
CTCF Promotes Muscle Differentiation by Modulating the Activity of Myogenic Regulatory Factors
复制标题
DOI：
10.1074/jbc.m110.164574
复制
发表时间：
2011-04-08
影响因子：
4.8
通讯作者：
Recillas-Targa, Felix
中科院分区：
文献类型：
--
作者：
Delgado-Olguin, Paul;Brand-Arzamendi, Koroboshka;Recillas-Targa, Felix
CTCF核因子调节基因表达的许多方面，主要是作为转录抑制因子或通过绝缘体功能。它在细胞分化中的作用尚不清楚。在这里，我们展示了一个意想不到的CTCF在肌肉发生中的作用。CTCF在小鼠和斑马鱼发育过程中的肌源性结构中表达。在C2C12细胞中，功能获得和功能丧失的方法表明，CTCF通过调节肌肉特异性基因的表达来调节肌肉发生。我们讨论了CTCF和肌源性调节因子(MRF)之间的功能联系。CTCF增强了MyoD和Mygenin的成肌潜能，并与MyoD建立了直接的相互作用，表明CTCF调节MRF介导的肌肉分化。事实上，CTCF调节MyoD和Mygenin之间的功能相互作用，共同激活肌肉特异性基因表达，并促进MyoD募集到肌肉特异性启动子。最后，CTCF在斑马鱼胚胎中的功能丧失实验揭示了CTCF在肌肉发育中的关键作用，并通过调节Wnt信号将CTCF与更广泛的发育方面联系起来。我们得出结论，CTCF在肌肉发生的协调中调节MRF功能的相互作用。
CTCF nuclear factor regulates many aspects of gene expression, largely as a transcriptional repressor or via insulator function. Its roles in cellular differentiation are not clear. Here we show an unexpected role for CTCF in myogenesis. Ctcf is expressed in myogenic structures during mouse and zebrafish development. Gain-and loss-of-function approaches in C2C12 cells revealed CTCF as a modulator of myogenesis by regulating muscle-specific gene expression. We addressed the functional connection between CTCF and myogenic regulatory factors (MRFs). CTCF enhances the myogenic potential of MyoD and myogenin and establishes direct interactions with MyoD, indicating that CTCF regulates MRF-mediated muscle differentiation. Indeed, CTCF modulates functional interactions between MyoD and myogenin in co-activation of muscle-specific gene expression and facilitates MyoD recruitment to a muscle-specific promoter. Finally, ctcf loss-of-function experiments in zebrafish embryos revealed a critical role of CTCF in myogenic development and linked CTCF to broader aspects of development via regulation of Wnt signaling. We conclude that CTCF modulates MRF functional interactions in the orchestration of myogenesis.