A Novel YY1-miR-1 regulatory circuit in skeletal myogenesis revealed by genome-wide prediction of YY1-miRNA network.

A Novel YY1-miR-1 regulatory circuit in skeletal myogenesis revealed by genome-wide prediction of YY1-miRNA network.
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DOI:
10.1371/journal.pone.0027596
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Wang H
Wang H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lu L;Zhou L;Chen EZ;Sun K;Jiang P;Wang L;Su X;Sun H;Wang H

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microRNA(miRNAs)是转录后调节基因表达的非编码RNA,越来越多的证据支持它们与转录因子(TF)相互作用的普遍性和功能意义。在这里,我们描述了肌肉miRNA(miR-1,miR-133和miR-206)和阴阳1(YY 1),一个骨骼肌发生的表观遗传阻遏物之间的调控回路的鉴定。通过结合计算预测和表达谱数据对YY 1潜在下游靶点的全基因组鉴定揭示了在骨骼肌成肌细胞分化为肌管期间YY 1的大量推定miRNA靶点,其中肌肉miR排名在列表的顶部。随后的实验结果表明,YY 1确实抑制成肌细胞中肌肉miR的表达,并且抑制是通过多个增强子和Polycomb复合物募集到几个YY 1结合位点介导的。YY 1调节miR-1在C2 C12肌源性分化和损伤诱导的肌肉再生中具有重要功能。此外,我们证明miR-1反过来靶向YY 1,从而形成负反馈环。总之,这些结果确定了骨骼肌发生所需的一种新的调节回路,并加强了涉及miRNA和TF的调节回路是普遍机制的观点。
microRNAs (miRNAs) are non-coding RNAs that regulate gene expression post-transcriptionally, and mounting evidence supports the prevalence and functional significance of their interplay with transcription factors (TFs). Here we describe the identification of a regulatory circuit between muscle miRNAs (miR-1, miR-133 and miR-206) and Yin Yang 1 (YY1), an epigenetic repressor of skeletal myogenesis in mouse. Genome-wide identification of potential down-stream targets of YY1 by combining computational prediction with expression profiling data reveals a large number of putative miRNA targets of YY1 during skeletal myoblasts differentiation into myotubes with muscle miRs ranking on top of the list. The subsequent experimental results demonstrate that YY1 indeed represses muscle miRs expression in myoblasts and the repression is mediated through multiple enhancers and recruitment of Polycomb complex to several YY1 binding sites. YY1 regulating miR-1 is functionally important for both C2C12 myogenic differentiation and injury-induced muscle regeneration. Furthermore, we demonstrate that miR-1 in turn targets YY1, thus forming a negative feedback loop. Together, these results identify a novel regulatory circuit required for skeletal myogenesis and reinforce the idea that regulatory circuitries involving miRNAs and TFs are prevalent mechanisms.
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