Genome-wide survey by ChIP-seq reveals YY1 regulation of lincRNAs in skeletal myogenesis
Genome-wide survey by ChIP-seq reveals YY1 regulation of lincRNAs in skeletal myogenesis
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DOI：
10.1038/emboj.2013.182
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发表时间：
2013-10-02
期刊：
影响因子：
11.4
通讯作者：
Wang, Huating
中科院分区：
文献类型：
--
作者：
Lu, Leina;Sun, Kun;Wang, Huating
骨骼肌分化是由转录因子、表观遗传调节因子和非编码RNA组成的网络。转录因子阴阳1(YY1)通过招募Ezh2(Zust Homologue2的增强子)来沉默成肌细胞(MBS)中的多个靶基因。为了阐明MBS中YY1的全基因组结合，我们进行了染色质免疫沉淀(ChIP)-SEQ，在MBS中发现了1820个特异结合位点，其中很大一部分位于基因间隔区。详细的分析表明，YY1除了具有已知的抑制因子功能外，还可以作为许多基因座的激活子。YY1和Ezh2之间没有发现显著的共占，这表明YY1在MBS中具有额外的Ezh2不依赖的功能。对基因间结合位点的进一步分析表明，YY1潜在地调控着数十个大的基因间非编码RNA(LincRNAs)，其在肌肉发生中的功能尚未得到充分的研究。我们鉴定了一个受YY1正调控的新的肌肉相关lincRNA(YAM-1)。YAM-1在分化过程中下调，并作为肌肉生成的抑制因子。我们证明了YAM-1通过对miR-715的顺式调节发挥作用，miR-715进而靶向Wnt7b。我们的发现不仅提供了肌肉细胞中YY1关联的第一张全基因组图像，而且还揭示了lincRNA Yam-1的功能作用。
Skeletal muscle differentiation is orchestrated by a network of transcription factors, epigenetic regulators, and non-coding RNAs. The transcription factor Yin Yang 1 (YY1) silences multiple target genes in myoblasts (MBs) by recruiting Ezh2 (Enhancer of Zeste Homologue2). To elucidate genome-wide YY1 binding in MBs, we performed chromatin immunoprecipitation (ChIP)-seq and found 1820 specific binding sites in MBs with a large portion residing in intergenic regions. Detailed analysis demonstrated that YY1 acts as an activator for many loci in addition to its known repressor function. No significant co-occupancy was found between YY1 and Ezh2, suggesting an additional Ezh2-independent function for YY1 in MBs. Further analysis of intergenic binding sites showed that YY1 potentially regulates dozens of large intergenic non-coding RNAs (lincRNAs), whose function in myogenesis is under-explored. We characterized a novel muscle-associated lincRNA (Yam-1) that is positively regulated by YY1. Yam-1 is downregulated upon differentiation and acts as an inhibitor of myogenesis. We demonstrated that Yam-1 functions through in cis regulation of miR-715, which in turn targets Wnt7b. Our findings not only provide the first genome-wide picture of YY1 association in muscle cells, but also uncover the functional role of lincRNA Yam-1.