组蛋白甲基化是一类重要的表观遗传修饰，参与多种生物过程的调控。已知组蛋白H3和H4上主要有六个赖氨酸甲基化位点，但仍有部分位点尚未鉴定，功能不明确。我们的前期工作中发现在多类真核生物体内H3K14位点存在三甲基化修饰（H3K14me3），这一发现已在少量文献中偶有提及，但对于其基因组定位、调控酶和所发挥的生物学功能的理解仍处于空白。我们推测H3K14me3很可能携带有未知的表观遗传信息并与其它表观遗传修饰相互通话(crosstalk)从而发挥其功能。为了阐明对该位点甲基化修饰的功能及调控机制，本项目将研究细胞中该位点的三种甲基化状态，采用ChIP-seq确定H3K14甲基化在基因组上的定位特征，分析它们与其它表观遗传修饰的关系，并寻找该位点的甲基化酶。本课题将有助于揭开这类未知的组蛋白修饰的生物学功能并完善对组蛋白甲基化调控体系的理解。

Histone methylation plays crucial role in epigenetic regulation of many biological processes. There are six well-known major lysine(K) methylation sites on histone H3 and H4, however, studies also have uncovered several other lysine methylation sites on Histone H3, including H3K14. H3K14 trimethylation (H3K14me3), noted previously in a couple of large-scale proteomics studies, has also been identified in several type of eukaryotic cells from our recent effort. However, its genome-wide distribution pattern, corresponding methyltransferase(s), and biological function are still lacking. In this proposal, We hypothesize that H3K14me3 represents a type of novel histone modification, carries unknown epigenetic information and plays its role through crosstalking with other modifications. In this study, we will determine whether all three forms of methylation exist on H3K14, analyze their functional relationship with other modifications and determine specific methyltransferase(s) that catalyzes the addition of methyl groups on this site. The completion of this study will reveal the biological function of H3K14 methylation and improve our knowledge on the regulatory system of histone methylation.