MARVELD1调节组蛋白H4k20me1影响小鼠内胚层细胞迁移及上皮细胞分化的分子机制

内胚层细胞分化发育的表观遗传调控是发育、肿瘤发生及干细胞研究的热点问题，但因机制复杂，诸多问题尚待阐明。本项目将在已获得的MARVELD1与H4K20me1相互作用，以及MARVELD1随内胚层细胞分化表达增强而其敲除后细胞迁移紊乱、增殖异常等前期研究基础上，以内胚层细胞迁移与消化管上皮成熟分化为切入点，利用已建立的MARVELD1敲除鼠模型和ES细胞模拟体系，采用免疫组化与免疫荧光、原位杂交、Co-IP、表达谱分析和ChIP-seq等技术，研究MARVELD1与H4K20me1互作调控内胚层细胞迁移与分化的分子基础，揭示MARVELD1调节H4K20me1表观修饰影响内胚层发育中ITGB1和ITGB4表达平衡、以及与上皮间质转化的作用，建立基于MARVELD1—H4K20me1互作的内胚层细胞分化发育的调控通路，为认识表观调控与内胚层细胞分化发育和功能关系提供新的证据。

Epigenetic regulation in endothelial cell differentiation and development has become a research hotspot of development, tumorigenesis and stem cell. However, the detailed mechanism remains obscure due to its complexity. Our preliminary work demonstrated that MARVELD1 interacts with H4K20me1, and revealed that MARVELD1 expression was up-regulated during endodermal differentiation. Moreover, MARVELD1 knockout led to abnormal cell migration and proliferation. Accordingly, here we attempt to clarify the molecular mechanism between MARVELD1，H4K20me1 and ITGB1-ITGB4 patterns during early endoderm development by using immunochemistry, immunofluorescence, in situ hybridization, Co-IP, gene expression profiles analysis and Chip-seq, based on MARVELD1 conditional knockout mice as in vivo model and ES differentiation in vitro. Additionally, the endodermal differentiation regulated pathway mediated by interaction between MARVELD1 and H4K20me1 will be depicted. This project will provide new insights for understanding the histone epigenetic modification in endodermal development.