鸡生长激素受体基因天然反义链转录本调控正义链转录本的机理解析及其在成肌细胞分化中的作用

动物体内能转录出与功能基因mRNA反向的转录本，即天然反义链转录本。其常通过互补序列区发挥功能。生长激素受体基因（GHR）是动物生长轴中的关键基因。我们前期研究发现鸡GHR基因双向转录，并克隆了与已知GHR mRNA（GHR-S）反向的反义链转录本GHR-AS；干扰等实验表明，GHR-AS影响GHR-S的转录。但是GHR-AS调控GHR-S的机制及其生物学功能尚不清楚。本项目拟在前期基础上，采用ChIP等方法开展以下研究：①GHR-AS调控GHR-S的表观遗传学机制；②GHR-AS与Let-7b是否竞争性结合GHR-S的3′UTR区，从而调控GHR-S；③GHR-AS对成肌细胞分化的影响。通过上述研究将阐明GHR-AS调控GHR-S的机理，揭示其在成肌细胞分化过程中的作用。研究结果将丰富GHR基因的调控通路，为动物基因复杂调控机制研究提供基本数据和参考，为家禽发育调控提供依据。

More and more researches indicated that a lot of genes can be transcribed in double directions. It means that one gene not only possessed the sense transcript but also had the natural antisense transcript（Nat）. Growth hormone receptor (GHR) gene plays important roles in animal growth. The dwarf chicken is due to the mutations of GHR gene. In our former study, we found chicken GHR gene can be transcribed in both directions and cloned its natural antisense transcript (GHR-AS). Further study showed that GHR-S fluctuated with the change of GHR-AS in the RNAi and the other experiments. However, how the GHR-AS regulates the GHR-S and functions in animal growth remain unknown. Based on the previous results, we would carry out the following work with ChIP and the other technologies: (1) How GHR-AS regulates GHR-S by epigenetic mechanism? (2) Whether GHR-AS and Let-7b competitively combine with GHR-S via the 3′UTR of GHR gene; (3) How GHR-AS functions in the myoblast differentiation. The mechanism of GHR-AS regulating GHR-S and the roles of GHR-AS in the myoblast differentiation could be clarified though the above researches. This study will be beneficial in understanding GHR function and will be helpful in revealing complex gene regulation network. Furthermore, the implementation of this project will provide important information for molecular breeding in chicken growth.