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Genome-wide survey by ChIP-seq reveals YY1regulation of lincRNAs in skeletal myogenesis

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摘要 : Skeletal muscle differentiation is orchestrated by a networkof transcription factors, epigenetic regulators, and noncodingRNAs. The transcription factor Yin Yang 1 (YY1)silences multiple target genes in myoblasts (MBs) byrecruiting Ezh2 (Enhancer of Zeste Homologue2).
Abstract: Skeletal muscle differentiation is orchestrated by a networkof transcription factors, epigenEtic regulators, and noncodingRNAs. The transcription factor Yin Yang 1 (YY1)silences multiple target genes in myoblasts (MBs) byrecruiting Ezh2 (Enhancer of Zeste Homologue2). Toelucidate genome-wide YY1 binding in MBs, we performedchromatin immunoprecipitation (chip)-seq and found 1820specific binding sites in MBs with a large portion residing inintergenic regions. Detailed analysis demonstrated that YY1 acts as an activator for many loci in addition to itsknown repressor function. No significant co-occupancywas found between YY1 and Ezh2, suggesting an additionalEzh2-independent function for YY1 in MBs. Furtheranalysis of intergenic binding sites showed that YY1potentially regulates dozens of large intergenic non-codingRNAs (lincRNAs), whose function in myogenesis is underexplored.We characterized a novel muscle-associatedlincRNA (Yam-1) that is positively regulated by YY1.Yam-1 is downregulated upon differentiation and acts asan inhibitor of myogenesis. We demonstrated that Yam-1functions through in cis regulation of miR-715, which inturn targets Wnt7b. Our findings not only provide the firstgenome-wide picture of YY1 association in muscle Cells, butalso uncover the functional role of lincRNA Yam-1. 原文链接:http://www.ncbi.nlm.nih.gov/pubmed/23942234/ 作者:广州赛诚生物 点击:
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