蛋白甲基化修饰系统对于基因组精密转录至关重要，蛋白甲基化酶和去甲基化酶通过对组蛋白动态修饰调控基因转录是表观遗传学“组蛋白密码子学说”的核心内容之一，其失调会导致包括癌症在内的多种疾病的发生。众所周知，基因转录也受到转录因子的精密调控。然而，甲基化修饰系统如何通过以转录因子为代表的非组蛋白底物调控基因转录的模式还不完全清楚。本项目选择以YY2为代表的转录因子为研究对象，以申请团队在“非组蛋白底物甲基化修饰”方面的大量前期研究为基础，研究转录因子YY2受甲基化修饰系统调控的分子机制及其探讨该机制在癌症发生发展中的作用，以期系统地阐述以YY2为中心的表观遗传调控网络，拓展“非组蛋白密码子”的研究。

Post translational modifications, such as methylation, and the enzymes involved in such modifications, have been proved to be crucial for a variety of biological processes, including gene transcriptional control. Methylation on histone proteins, which is dynamically regulated by protein methyltransferases and demethylases, is a central part of “histone code” in epigenetics. Dysregulation of the methylation machinery can lead to a variety of diseases, such as cancers. It is also well known that gene transcription is precisely regulated by proteins called transcription factors. However, whether these transcription factors can serve as substrates of the methylation machinery, and the molecular mechanisms underlying regulation by methylation remain incompletely understood. YY2, the homolog of YY1 in human, has been proposed to function redundantly or oppositely in a context specific manner compared to YY1. In the present proposal, based on our preliminary data that YY2 was methylated, we aimed to identify the methyltransferase and demethylase involved in YY2 methylation, and investigate the molecular mechanisms underlying YY2 methylation in gene transcriptional control and therefore its implication in cancer development. Through the proposed study, we aimed to further expand the repertoire of non-histone substrates and better understand the “non-histone code” in epigenetics.