胚胎基因组启动（EGA）对哺乳动物植入前胚胎发育至关重要。DUX4作为先锋因子，在EGA早期快速激活表达的机制仍不清楚。DUX4位于亚端粒区域，在疾病中的研究提示其表达受端粒位置效应（TPE）调控。课题组前期研究发现，早期胚胎的DUX4表达呈现母源性偏斜，且小鼠胚胎在EGA初期表达DUX4同源基因Dux的同时伴随端粒长度出现一过性缩短现象；结合既往研究发现胚胎母源基因组端粒明显短于父源基因组。课题组提出假设：卵母细胞在受精后端粒的一过性缩短过程中通过更早的解除TPE，优先激活母源性DUX4表达启动了EGA过程。为证实这一假设，拟通过确证DUX4的母源性启动及其对胚胎发育的影响，探索DUX4基因TPE解除的关键因素，构建EGA过程中DUX4启动的途径及分子机制，为临床胚胎发育阻滞原因分析提供新思路。

Embryo genome activation (EGA) is a central event in mammalian pre-implantation embryo development. As a pioneer factor of EGA, the mechanism of rapid activation of DUX4 transcription in early development remains unclear. Studies in diseases have shown that DUX4 gene is located in the sub-telomere region of the chromosome and its expression is affected by telomere location effect (TPE). Our previous study found DUX4 transcription exhibited a maternal skew and Dux homologous gene activation in the 2-cell embryo of mouse EGA process accompanied by a temporary shortening of telomere length. In addition, the telomeres of the maternal genome in mouse embryos were significantly shorter than those of the parent genome. Based on these observations, we propose that transient telomere shortening during early embryonic development preferentially initiates maternal DUX4 expression by releasing maternal genome TPE and triggers EGA. In order to verify this hypothesis, we will trace the initiation of DUX4/Dux and its effect on embryonic development, to explore the molecular mechanism of TPE release of DUX4 gene in mouse embryos. This study would provide novel molecular mechanisms for mammalian EGA and new ideas for exploring of the causes of embryo arrest.