Sprott Center for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, CA.
Epigenetics. 2010 Nov-Dec;5(8):691-5. doi: 10.4161/epi.5.8.13045. Epub 2010 Nov 1.
MyoD is a master regulator of the skeletal muscle gene expression program. ChIP-Seq analysis has recently revealed that MyoD binds to a large number of genomic loci in differentiating myoblasts, yet only activates transcription at a subset of these genes. Here we discuss recent data suggesting that the ability of MyoD to mediate gene expression is regulated through the function of Polycomb and Trithorax Group proteins. Based on studies of the muscle-specific myog gene, we propose a model where the transcriptional activators Mef2d and Six4 mediate recruitment of Trithorax Group proteins Ash2L/MLL2 and UTX to MyoD-bound promoters to overcome the Polycomb-mediated repression of muscle genes. Modulation of the interaction between Ash2L/MLL2 and Mef2d by the p38α MAPK signaling pathway in turns provides fine-tuning of the muscle-specific gene expression program. Thus Mef2d, Six4, and p38α MAPK function coordinately as regulators of a master regulator to mediate expression of MyoD target genes.
MyoD 是骨骼肌基因表达程序的主要调节因子。最近的 ChIP-Seq 分析表明，MyoD 在分化的成肌细胞中结合到大量基因组位置，但仅在这些基因的一部分中激活转录。在这里，我们讨论了最近的数据，这些数据表明 MyoD 介导基因表达的能力是通过 Polycomb 和 Trithorax 组蛋白的功能来调节的。基于对肌肉特异性 myog 基因的研究，我们提出了一个模型，其中转录激活因子 Mef2d 和 Six4 介导 Trithorax 组蛋白 Ash2L/MLL2 和 UTX 招募到 MyoD 结合的启动子上，以克服肌肉基因的 Polycomb 介导的抑制。p38α MAPK 信号通路对 Ash2L/MLL2 和 Mef2d 之间相互作用的调节反过来又为肌肉特异性基因表达程序提供了精细的调节。因此，Mef2d、Six4 和 p38α MAPK 作为一个主要调节因子的调节因子共同作用，介导 MyoD 靶基因的表达。
