在个体发育和细胞分化过程中，细胞谱系特异的转录因子通过调控靶基因的表达决定细胞命运，而这类转录因子是如何调控靶基因的特异性表达的分子机制仍不是十分清楚。近年来,随着细胞特异性表达的长非编码RNA的不断发现和其在基因表达调控中的表观遗传学功能的发现，提示长非编码RNA可能与特异性转录因子相互协同调控靶基因表达的特异性。本实验室前期研究发现一个骨骼肌组织特异表达的lncRNA（Linc-MCD）与转录因子MyoD结合，影响MyoD调控靶基因的特异性，并通过增加染色质重塑酶Brg1的募集促进细胞分化。本项目的核心是深入探讨与MyoD结合的Linc-MCD调控MyoD功能及其靶基因特异性的分子机制，并采用Linc-MCD转基因和敲除鼠在体内进一步验证Linc-MCD对MyoD功能的重要性及其对骨骼肌发育与疾病的调控作用。本项目将为其他转录因子调控靶基因特异性的分子机理研究提供参照。

ENCODE project demonstrates that eukaryotic genome encodes a substantial number of long non-protein coding RNA (lncRNAs), which significantly advance the knowledge about human genome function. As growing body of convincing evidence show the involvement of lncRNAs in the epigenetic regulation of gene transcription, the scientists have recently paid more attention and raised particular interest in the expressional regulation of genes. Although it has long been appreciated that cell lineage specific transcriptional factor play critical role in the cell lineage commitment and differentiation, we actually know little about how the functional specificity of the transcriptional factors is achieved.Based on current information of lncRNA functional studies, especially more and more tissue specific lncRNAs have been identified, it is conceivable that tissue or cell lineage specific lncRNAs may concert with transcriptional factors to regulate their functional specificity on target gene expression. Recently, we have identified a skeletal muscle specifically expressed intergenic lncRNA which is required for muscle cell differentiation, hereafter named as Linc-MCD. Our experimental data demonstrate that Linc-MCD binds MyoD and possibly involves its functional specificity on the target gene expression. Therefore, we have a great interest to further investigate the molecular mechanism of the Linc-MCD in regulating functional specificity of MyoD during muscle cell differentiation as we have proposed in this proposal. Significantly, the function of the Linc-MCD/MyoD interaction will be further corroborated in vivo using Linc-MCD transgenic and knockout mice. Our findings from the proposed work will not only provide a paradigm for the investigations of the functional specificity of other transcriptional factors, but also provide an additional mechanism of lncRNA function in regulating gene transcription in which lncRNA functions to regulate gene expression by directly binding with transcriptional factor.