组蛋白去甲基化酶KDM5家族在牛母源-胚胎转换期间的作用及机制

早期胚胎丢失是造成奶牛和肉牛繁殖率低下的主要原因之一。早期胚胎发育过程中一个重要特征是母源-胚胎转换，在这一过程中表观遗传重编程发挥着重要作用，但机制尚不清楚。在前期面上项目的资助下，我们解析了组蛋白甲基化H3K4me3的识别因子CHD1在牛早期胚胎发育中的重要作用和机制。近期，我们通过低起始量ChIP-seq技术发现H3K4me3在牛早期胚胎染色质上的分布呈现动态变化，组蛋白去甲基化酶KDM5的缺失阻碍牛早期胚胎发育，但是作用机理不明。本项目拟通过体外受精、显微注射RNA、低起始量ChIP-seq和RNA-seq等技术揭示牛母胚转换过程中KDM5的具体作用，阐明KDM5介导的H3K4me3去甲基化对基因表达的影响和机制，进而探讨KDM5对其他表观遗传重编程的影响和机制。本项目的研究有助于深化我们对牛早期胚胎发育过程中表观遗传调控的理解，为减少早期胚胎丢失，实现牛繁殖力的提升提供理论支持。

Early embryonic loss is a major factor resulting in poor reproductive efficiency in both dairy and beef cattle. Maternal-embryonic transition is one of the most important features of early embryonic development. Epigenetic reprogramming plays a critical role during maternal-embryonic transition. Nonetheless, the regulatory mechanisms remain unclear. Previously, we have determined that the genomic distribution of histone H3 lysine 4 tri-methylation (H3K4me3) is dynamic during embryonic genome activation in bovine early embryos. We also found knockdown of KDM5 (histone demethylase) led to a decrease in the developmental potential of bovine early embryos. However, the mechanisms behind these phenomena have yet to be determined. By employing a series of state-of-the-art techniques including low-cell ChIP-seq, RNA-seq, IVF and microinjection of RNA, the proposed studies will address the specific role of KDM5 during maternal-embryonic transition and mechanisms involved, determine the influences of KDM5-mediated H3K4me3 demethylation on gene expression globally during maternal-embryonic transition, and explore if KDM5 plays a role in reprograming of other epigenetic information. The proposed studies will better our understanding of the epigenetic control of bovine early embryonic development, help to reduce early embryo loss and increase reproductive efficiency in both dairy and beef cattle.