表观遗传学领域的核心课题之一是研究组蛋白修饰的writer/eraser/reader如何参与基因转录调控、DNA复制、损伤等染色质相关分子事件。转录抑制因子CDYL蛋白N端有参与赖氨酸甲基化识别的chromodomain，C端有可以结合烯酰辅酶A的CoAP domain，这种独特的结构域组成使其可能同时具有对多种组蛋白修饰的识别和编写功能。我们前期的研究工作证明CDYL可以与组蛋白H3赖氨酸27位二、三甲基化(H3K27me2/3)及其催化酶PRC2复合体直接相互作用，建立正反馈机制促进H3K27me3的形成。CDYL还参与H3K9me2/3在核小体间的传播。在以上分子基础上，本课题进一步研究CDYL如何影响与细胞功能分化密切相关的组蛋白甲基化修饰在复制期的保留和遗传，并探讨CDYL调控一种新型组蛋白修饰- - 组蛋白巴豆酰化（亦即组蛋白丁烯酰化）的生成机制及生物学功能。

Post-translational modifications of histones play important roles in mediating chromatin-based events such as gene transcription and DNA repair. Therefore the inheritance of histone modifications is important to maintain cell identity and proper cell function. Clarification of the molecular mechanisms underlying the modification installation, removal and/or interpretation is the central theme in the research of epigenetics. Transcriptional repressor CDYL contains an N-terminal chromodomain, which could bind to methylated lysine residues in histones and mediate chromatin-related functions. In addition, CDYL has a C-terminal enoyl-coenzyme A (CoAP) hydratase-isomerase catalytic domain, the function of which remains unknown. We have previously demonstrated that CDYL directly interacts with di- and tri-methylated lysine 27 of histone H3 (H3K27me2/3), and the polycomb repressive complex 2 (PRC2), the methyltransferase of H3K27me2/3. CDYL therefore acts as a molecular bridge to generate a positive feedback and facilitate the establishment and propagation of H3K27me3 modifications along the chromatin. Accordingly, we will further study how CDYL participates in the inheritance of H3K27me3, the key epigenetic mark to maintain differentiated cell-specific function. In addition, while we were able to demonstrate the CoAP domain of CDYL is able to bind crotonyl-coenzyme A, we will study the role of CDYL in regulating the generation of a newly discovered histone modification - crotonylation.