ERK5 Regulates Muscle Cell Fusion through Klf Transcription Factors
ERK5 Regulates Muscle Cell Fusion through Klf Transcription Factors
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DOI：
10.1016/j.devcel.2010.12.005
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发表时间：
2011-02-15
影响因子：
11.8
通讯作者：
Nishida, Eisuke
中科院分区：
文献类型：
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作者：
Sunadome, Kazunori;Yamamoto, Takuya;Nishida, Eisuke
在骨骼肌分化中，肌肉特异性基因受到两组转录因子MyoD和MEF 2家族的调节，它们共同作用以驱动分化过程。在这里，我们表明，ERK 5调节肌细胞融合通过Klf转录因子。抑制ERK 5活性可抑制肌细胞融合，对MyoD、MEF 2及其靶基因的表达影响最小。结合微阵列分析的启动子分析揭示Klf结合基序高度富集在ERK 5依赖性上调基因的启动子区域中。值得注意的是，Klf 2和Klf 4表达在分化期间也以ERK 5依赖性方式上调，并且Klf 2或Klf 4的敲低特异性抑制肌细胞融合。此外，我们表明，Sp1转录因子连接ERK 5 Klf 2/4，和肾连蛋白，Klf转录靶点，参与肌细胞融合。因此，ERK 5/Sp1/Klf模块在骨骼肌分化过程中的融合过程中起着关键作用。
In skeletal muscle differentiation, muscle-specific genes are regulated by two groups of transcription factors, the MyoD and MEF2 families, which work together to drive the differentiation process. Here, we show that ERK5 regulates muscle cell fusion through Klf transcription factors. The inhibition of ERK5 activity suppresses muscle cell fusion with minimal effects on the expression of MyoD, MEF2, and their target genes. Promoter analysis coupled to microarray assay reveals that Klf-binding motifs are highly enriched in the promoter regions of ERK5-dependent upregulated genes. Remarkably, Klf2 and Klf4 expression are also upregulated during differentiation in an ERK5-dependent manner, and knockdown of Klf2 or Klf4 specifically suppresses muscle cell fusion. Moreover, we show that Sp1 transcription factor links ERK5 to Klf2/4, and that nephronectin, a Klf transcriptional target, is involved in muscle cell fusion. Therefore, an ERK5/Sp1/Klf module plays a key role in the fusion process during skeletal muscle differentiation.