新型组蛋白巴豆酰化修饰调控因子的鉴定及其在体细胞重编程中的作用

Histone post-translational modifications (PTMs) can modulate chromatin structure and are known to regulate a wide variety of cellular processes such as gene transcription, cell differentiation and development. With recent advances in mass spectrometry, several novel types of histone acylation have been identified, including propionylation, butyrylation, crotonylation. It has been shown that in male germinal cells immediately following meiosis, histone crotonylation (Kcr) is specifically enriched on sex chromosomes and marks X/Y-linked genes that escape inactivation. Our research team recently identified a novel class of histone crotonylation regulators which are expressed at particuliar phases during early embroynic development. We plan to carry out structure and functional characterizations of these novel epigenetic regulators in order to elucidate their roles in early development and cell reprogramming. Their impact on somatic cell reprogramming will also be evaluated by functional pertubation of these factors.

组蛋白翻译后修饰可以通过改变染色质结构和招募下游因子，参与调控基因表达、细胞分化和发育等重要生命过程。近年随着功能质谱技术手段的改进，越来越多新型组蛋白酰基化修饰类型及其重要作用被报道，如丙酰化、丁酰化、巴豆酰化等。已知巴豆酰化在配子生成减数分裂后期特异标记性染色体相关基因，使其逃避基因沉默。项目申请人团队新近鉴定出一类新型组蛋白巴豆酰化识别调控因子，而且这些因子在早期胚胎发育特定阶段表达。本项目拟针对这些新型表观遗传调控因子开展结构与功能研究，阐明其在早期胚胎发育和体细胞重编程过程中发挥作用的生化分子机制，并探讨对这些因子的干预在优化体细胞重编程体系中的作用效果。

组蛋白翻译后修饰可以通过改变染色质结构和招募下游因子,参与调控基因表达、细胞分化和发育等重要生命过程。近年随着功能质谱技术手段的改进,越来越多新型组蛋白酰基化修饰类型及其重要作用被报道,如丙酰化、丁酰化、巴豆酰化，beta羟基丁酰等，这些修饰与内外环境、物质和能量代谢密切相关，是领域内研究的热点。已知巴豆酰化在配子生成减数分裂后期特异标记性染色体相关基因,使其逃避基因沉默。项目申请人团队鉴定出两类新型组蛋白巴豆酰化识别阅读器YEATS结构域和双锌指DPF结构域,针对这些新型表观遗传调控因子开展了系统的结构与功能研究,阐明了YEATS在炎症反应和免疫应答中发挥作用的生化分子机制,并正在研究组蛋白巴豆酰化及其阅读器蛋白在早期胚胎发育中的作用及分子机制。我们的研究大大加速了代谢如何通过影响组蛋白酰基化调控靶基因表达程序的研究的进程。