泛癌染色质调控子协同互作网络构建及其表观遗传调控机制研究

Chromatin regulators are indispensable upstream regulatory factors of epigenetic modifications and are found to mediate the epigenetic modifications to regulate the biological processes and the development of cancers. Recent studies showed that chromatin regulators could mediate the epigenetic modifications by synergistic interactions, so as to precisely regulate biological processes such as gene transcription. Therefore, identification of the genome-wide synergistic interactions between chromatin regulators and the further exploration of their synergistic regulation mechanisms are innovative and significant. This project intends to integrate a large-scale data on chromatin regulators and epigenetic modifications at the pan-cancer level, construct and dissect the chromatin regulators associated synergistic interaction networks through bioinformatics methods. Based on the synergistic networks across cancer types, we will excavate the conserved and specific synergistic modules, identify their regulatory epigenetic modifications and genes, and explore the commonness and difference of epigenetic regulation across cancer types. Finally, a bioinformatics analysis platform for functional assessment of the synergistic interactions between chromatin regulators will be established, to provide important insights for studies on synergistic interaction mechanism of chromatin regulators and epigenetic regulation in cancers, and provide new trends to diagnosis and treatment of cancers from the perspective of epigenetics.

染色质调控子（Chromatin Regulator）是表观遗传修饰的关键上游调控因子，通过介导表观修饰参与生命活动和癌症的发生发展历程。最新研究表明，染色质调控子可通过协同互作来介导多种表观修饰，实现精确调控基因转录等生物过程的目的。因此，全基因组内识别染色质调控子的协同作用并解析其协同调控机制是一项具有创新性以及重要意义的工作。本项目拟整合大规模、癌症背景下的染色质调控子和表观修饰相关数据，采用生物信息学方法，构建染色质调控子协同互作网络，剖析其协同互作特点，挖掘泛癌保守和癌症特异的协同互作模块，确定其调控的表观修饰和基因，探索癌症表观遗传调控的共性和异质性。同时，建立泛癌染色质调控子协同互作的功能解析生物信息学平台，为染色质调控子协同互作机制和癌症表观遗传调控的研究提供重要依据，从表观遗传角度为癌症诊断和治疗提供新思路。

染色质调控子可通过协同互作来介导多种表观修饰，实现精确调控基因转录等生物过程的目的，从而介导癌症的发生发展过程。本项目以多种癌症为疾病模型，整合多个数据库资源中染色质调控子相关的ChIP-seq数据，构建癌症背景下的染色质调控子协同互作网络，识别不同癌症间保守的和特异的染色质调控子协同互作模块，解析协同互作的染色质调控子的作用特点，并结合细胞系或样本所属癌症信息，进一步阐明协同染色质调控子的保守和特异的作用机制。深入分析保守和特异模块的染色质调控子的重叠作用peak区域与基因元件位置的相关关系，从而揭示协同互作模块中染色质调控子的作用特点及潜在生物学意义。基于上述的癌症保守和特异的协同互作模块，融合不同类型表观修饰的数据，寻找协同互作的染色质调控子对所介导的表观修饰，深入挖掘下游基因相关生物学过程和通路，深化理解特异模块在特异癌症中的表观调控机制。. 此外，在顺利执行原计划的基础上，同时也对课题进行了深入的扩展研究，并取得了良好的研究结果。本项目的研究结果为癌症分子靶向治疗提供可靠的理论依据，具有潜在的临床意义，对探讨表观遗传机制、癌症发病机理、推进染色质调控子协同调控研究具有重大意义。本项目目前共发表SCI论文4篇（均标注了本项目号）。