牛早期胚胎发育期间CHD1作用的分子机制

奶牛繁殖率下降是影响奶牛养殖业平稳和可持续发展的主要问题之一。统计数据显示早期胚胎死亡是造成奶牛不孕的一个主要原因。早期胚胎发育阶段伴随着一系列重要的发育生物学事件的发生，如染色质重构等，但这些事件的调控机制尚未阐明。我们的前期研究发现染色质重构因子CHD1的缺失不仅造成牛早期胚胎发育率降低，还导致早期胚胎中重要的组蛋白变体H3.3的含量显著下降，但是其作用机制还不清楚。因此，本项目拟通过体外受精、显微注射siRNA等技术研究CHD1的缺失对牛早期胚胎中染色质组分、表观遗传修饰和H3.3伴侣蛋白HIRA复合物相关基因和蛋白的影响，揭示CHD1影响早期胚胎发育及调控H3.3的分子机制，并进一步探讨CHD1作为潜在的重编程因子在牛克隆胚胎发育过程中的作用和机制。本项目的研究将进一步加强我们对牛早期胚胎发育过程调控机制的理解，有助于采取相关措施提高奶牛早期胚胎的发育率，进而提高奶牛繁殖率。

Decreasing fertility in dairy cows is one of the major challenges impacting the sustainable development of the dairy cow industry. Early embryo loss is one of the major factors results in infertility in dairy cows. During early embryonic development, various developmental events are reprogrammed to ensure the successful embryonic development, including chromatin remodeling. However, it remains largely unknown regarding the regulatory mechanisms of these critical developmental events. Previously, we identified that knockdown of CHD1 (Chromodomain Helicase DNA Binding Protein 1) reduced developmental potential of bovine early embryos and decreased the deposition of the critical histone variant H3.3 in bovine early embryos. However, the molecular mechanism underlying the CHD1’s effects in bovine early embryos is yet to be defined. The proposed studies will address 1) the intrinsic role of CHD1 and the underlying mechanism in chromatin remodeling and epigenetic reprogramming after fertilization, 2) if CHD1 regulates H3.3 deposition by modulating HIRA complex and 3) the role of CHD1, as a candidate reprogramming factor, in the development of somatic cell nuclear transfer embryos. The proposed research will increase our understanding of the molecular control of bovine early embryonic development and serve as the foundation on which future studies may be built to develop solutions to reduce early embryo loss or improving pregnancy rate in dairy cows.