叶酸缺乏参与多系统先天畸形的发生，但机制不明。Brachyury基因作为早期胚胎发育关键调控网络中的核心因子，该基因功能丧失可导致来自不同胚层的多个组织器官畸形。前期发现叶酸缺乏致Brachyury基因表达显著下调及启动子区高甲基化，且叶酸回补能有效逆转。据此我们提出叶酸缺乏通过表观调控因子复合物调控Brachyury的表观修饰状态，导致其表达下调，引起多系统发育异常。本研究拟利用叶酸缺乏的三胚层细胞模型，通过EMSA和DNA pulldown/MS明确参与调控Brachyury的表观因子；ChIP-qPCR和Luciferase明确叶酸缺乏致Brachyury表达异常的表观作用机制；结合Brachyury敲除的动物模型，评价叶酸在体内外缺乏条件下Brachyury异常表达对多系统胚胎发育的影响，及增补叶酸对异常胚胎发育的逆转效应，为叶酸缺乏干扰多系统发育的调控机制和作用靶点提供实验依据。

Folate deficiency participates in multisystem congenital malformation, but the mechanism remains unclear. Brachyury gene is the core factor in the critical regulatory network of early embryonic development, and loss of its function can lead to multiple organ malformations from different germ layers. Our previous research found that folate deficiency caused the down-regulation of Brachyury gene expression and hypermethylation of promoter region, and folate supplementation could effectively reverse it. In view of the above，we propose that folate deficiency regulates the epigenetic modification of Brachyury by epigenetic regulatory factor complex, resulting in its down-regulation of Brachyury expression , which leads to multiple system development abnormalities. In this study, we intend to use a triploblastic cell model of folate deficiency to identify the epigenetic modification factors involved in the regulation of Brachyury by the methods of EMSA and DNA pulldown/MS, and to identify the epigenetic mechanism of folate deficiency affecting the abnormal expression of Brachyury by the methods of ChIP-qPCR and Luciferase. Combined with the animal model of Brachyury knockout, we evaluate the effect of abnormal Brachyury expression on the multisystem embryonic development under the condition of folate deficiency in vivo and vitro. Meanwhile we evaluate the reverse effect of folic acid supplementation on the abnormal embryonic development. Our study provides experimental basis for the regulation mechanism and target of folate deficiency interfering with multisystem development.