基于高通量数据挖掘揭示染色质调控因子新的作用机制

表观遗传信息的编码和解码是由多种染色质调控因子在染色体上协同作用完成的，因此揭示染色质调控因子的作用机制是理解真核生物基因转录调控的重要环节。随着高通量生物学数据的快速积累，通过数据挖掘推断染色质调控因子潜在的作用底物或产物及染色质调控因子与其它因子的协同作用机制成为可能；然而国际上的相关研究还非常初步。近期，申请人基于收集和整理的哺乳动物公共ChIP-seq数据，通过高通量数据的整合与挖掘发现了染色质调控因子SetDB1在小鼠胚胎干细胞中新的作用机制。在此基础上，本项目提出通过发展通用的生物信息学方法，并结合实验验证，从高通量ChIP-seq数据中系统性地揭示染色质调控因子新的作用机制。本项目的研究将有助于高效识别染色质调控因子在特定生物学过程中所起的作用，为深入研究重要生物学过程中的表观遗传调控机制提供帮助。

In eukaryotic chromatin, as epigenetic information is encoded and decoded through the combination function of multiple chromatin regulators, revealing the functional mechanisms of chromatin regulators is of great significance to understand the regulation of gene transcription. With the rapid accumulation of high-throughput biological data, it has become possible to identify the unknown function of chromatin regulators through data mining, including the chromatin regulators' potential substrate or products, and the potential cooperation mechanisms between chromatin regulators and other factors. However, such studies are still very preliminary. Recently, based on the public mammalian ChIP-seq data we curated and collected, the novel functional mechanism of a chromatin regulator, SetDB1, in mouse embryonic stem cell was revealed through high-throughput data integrating and mining. On the basis of our previous studies, we propose to develop universal bioinformatics approaches, and together with experimental validation, to systematically reveal the novel functional mechanisms of chromatin regulators. This project will benefit the identification of chromatin regulators' function in certain biological process with high efficiency, and eventually help the studies of epigenetic regulatory mechanisms in important biological processes.