组蛋白新型表观遗传修饰的类型鉴定、功能研究、机制探索是表观遗传学研究的前沿内容。此前，我们揭示了组蛋白H3第79位赖氨酸琥珀酰化(H3K79succ)的修饰机制及其激活基因转录的功能。作为首个修饰机制已知的组蛋白琥珀酰化修饰位点，H3K79succ已成为基因转录激活的组蛋白表观遗传修饰标记，然而H3K79succ激活基因转录的机制尚不清楚。在前期工作的基础上，本课题将研究H3K79succ对核小体包装稳定性的调控，鉴定与H3K79succ结合的染色质构象调控因子和转录因子，从染色质构象调节和转录因子招募两方面分别解析H3K79succ激活基因转录的分子机制。上述机制将在临床肿瘤样品中验证以探索H3K79succ在肿瘤防治中的应用前景。本研究将深入探讨组蛋白琥珀酰化发挥生物学功能的机制，完善对组蛋白琥珀酰化表观遗传修饰的基本认识，为研究组蛋白琥珀酰化的基本规律及其临床应用提供重要参考。

The identification and studies of mechanism and functions of novel histone modifications are the raising fields in epigenetics. Given to our previous report about the modification mechanism and the gene transactivation function of histone H3 lysine 79 succinylation (H3K79succ), H3K79succ had been the first succinylation site on histone with known modification mechanism and function. Although H3K79succ has been proven as a new gene transactivation marker, the mechanism underlying H3K79succ regulating gene transcription is remaining elusive. Based on our published works and preliminary studies, we are proposing the present research plan to investigate the mechanism underlying H3K79succ regulating gene transcription. We will study the effects of H3K79succ on the assembly stability of nucleosome and identify the H3K79succ-associated proteins, focusing on chromatin conformational change/remodeling factors and transcriptional factors, which are expected to be used to understand the mechanism underlying H3K79succ-mediated gene transactivation in the aspects of chromatin conformation regulation and transcriptional factor recruitment. Additionally, the identified mechanism underlying H3K79succ-mediated gene transactivation will be validated in human tumor samples for future clinical applications of H3K79succ. The accomplishments of this proposed study will provide the first insight into the functional mechanism of histone H3K79succ, benefiting the studies of other histone succinylation sites and the future applications of histone succinylation in clinical practices.