曲古菌素A对人类体细胞核移植胚胎表观遗传重编程的影响

项目名称： 曲古菌素A对人类体细胞核移植胚胎表观遗传重编程的影响

项目编号： No.30800650

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 徐小明

作者单位： 中南大学

项目金额： 20万元

中文摘要： 人类体细胞核移植效率低下，核没有充分重编程被认为是核移植效率低的主要原因。核移植过程增加组蛋白乙酰化水平同时降低DNA甲基化水平，使得染色质结构松弛，DNA与组蛋白之间联系变的疏松，促进基因转录，有利于核充分重编程。本项目利用组蛋白去乙酰化酶抑制剂TSA处理人类体细胞核移植胚胎可明显提高核移植后桑囊胚发育率（30% vs 0），通过从DNA甲基化、组蛋白乙酰化、组蛋白甲基化水平及RNA转录活性几个层面比较与分析添加TSA与否的核移植胚胎和正常体外受精胚胎表观遗传重编程之间的差异，我们初步获得体细胞核移植早期事件中表观遗传重编程的一些规律，为进一步建立人类核移植来源的胚胎干细胞系奠定基础。

中文关键词： 体细胞核移植；表观遗传；重编程；TSA; 人类

英文摘要： The efficiency of human somatic cell nuclear transfer (SCNT) is very low. Major cause of low cloning efficiency may reside in incomplete reprogramming of somatic cell nucleus. Increased histone acetylation levels and decreased DNA methylation in the procedure of SCNT leads loose brinding of nuleosome to DNA and/or linker histones, relaxation of the chromatin structure, formation of transcriptionally permissive state and promotion of nucleus reprogramming. In this report, the efficiency of human SCNT can improve (30% vs 0) when the cloned embryos were treated with histone deacetylase inhibitor trychostatin A (TSA) for 16-18 h. The change in DNA methylation, histone acetylation levels and efficiency of reprogramming between IVF embryos and cloned embryos was analysis. We discovered some links between the evens of early of epigenetic reprogramming and the efficiency of human SCNT. Our research results may promote to establish human embryonic stem cells (ESCs) derived from SCNT.

英文关键词： somatic cell nuclear transfer; epigenetic; reprogramming; trychostatin A; human