长片段非编码RNA通过组蛋白的相互作用调控DMP1转录的分子机制研究

牙本质基质蛋白1（DMP1）在牙骨分化、成熟及矿化中有重要作用。DMP1基因调控机制尚不清楚。生物信息学分析及前期lncRNA芯片数据表明lncRNA对DMP1基因调控具有重要作用。DMP1调控机制现状分析发现，启动子和组蛋白乙酰转移酶活性在不同的时期可调控DMP1的基因表达。本课题提出lncRNA可能通过与组蛋白相互作用，形成复合物来共同调节DMP1基因表达。我们首先通过lncRNA芯片筛选，在不同组织和细胞中验证与DMP1 基因表达相关的lncRNA；再通过siRNA沉默或过表达与DMP1基因表达最相关lncRNA，阐明lncRNA对DMP1的mRNA表达的调控作用；最后通过RIP-Chip、EMSA和启动子双荧光酶素实验等分析手段，揭示lncRNA是否通过结合DMP1基因的启动子区并形成组蛋白复合物的分子机制来调控DMP1。明确DMP1调控机制可有目的、高效调控DMP1表达发挥其功能

Dentin Matrix protein 1 has very important roles in the adjusting mineralization of bone and dentin as well as the differentiation and maturation of the teenth and jaw.Since the mechanism of DMP1 gene's expression was not clear now,we will study on it. Base on the analysis of the bioinformatics DMP1 gene and our pre data of the lncRNA chips, we propose that lncRNA may has significant functions in the DMP1 gene adjustion. Studies show that the promoter and histone acetyltransferase may effect the DMP1 genen expression. We hypothesis that the DMP1 gene expression was regulated by long non-coding RNA-histone interaction. The lncRNAs which correlated with the DMP1's gene expression will obtain from the lncRNA chips data first, then they will be confirmed in different tissues and cell lines. To illiminate the effection of lncRNA in the DMP1 mRNA expression, the lncRNAs which correlated with DMP1 gene expression will be silence or overexpress in different cells lines. The RIP-Chip、EMSA and promoter renilla and luciferase activities were used to show whether the lncRNAs adjust the DMP1 gene expression by binding the DMP1 gene's promoter zone to form histone compound. Elucidate the mechanism of the regulation of DMP1 gene will has important functions in optional and efficient adjusting the DMP1 gene expression, furthmore to effect the teeth and bone differentiation, mineralization and mature.