中文摘要
rDNA基因的转录控制着细胞核糖体的生物合成,从而调控蛋白质的翻译。我们的前期研究表明体细胞rDNA活性影响了重编程的效率,提高rRNA转录有利于体细胞重编程。H3.3是与转录激活相关的组蛋白变体,其掺入父源染色质是早期胚胎发育的关键影响因素, H3.3也是体细胞核移植胚胎发育不可或缺的母源因子。DAXX介导的H3.3掺入rDNA染色质,从而开放rRNA转录可能是体细胞重编程的早期关键事件。本次申请旨在研究体细胞在核移植和诱导多潜能干细胞两种重编程过程中,H3.3掺入rDNA染色质区的动态变化及其表观修饰的改变,并研究 H3.3掺入使rDNA染色质开放对rRNA转录的影响。进一步通过调控H3.3掺入,促进rDNA转录,从而促进体细胞重编程效率。我们的研究对理解重编程中的组蛋白密码与rDNA活性的作用,提高重编程效率,促进核移植与诱导多潜能干细胞技术的应用具有重要意义。
英文摘要
Transcription of rDNA gene controls biosynthesis of the ribosome and regulates the translation of proteins in cell. Our previous studies indicated that efficiency of somatic cell reprogramming was affected by rDNA activity. And somatic cell reprogramming could be improved when rRNA transcription was increased. It is known that histone H3 variant H3.3 is related to active transcription, which incorprates into paternal chromatin is a critial factor involving in preimplantation embryonic development. Researches also demonstrated that H3.3 is an indispensable maternal factor for development of somatic cell nuclear transfer cloned embryos. DAXX mediating H3.3 incorporation into rDNA chromatin leads to opening state of the chromatin which might be the key event in early stage of somatic cell reprogramming. In the present study, we are going to investigate dynamic changes and epigenetic modification of histone variant H3.3 incorporating into rDNA chromatin during two reprogramming procesures, namely, somatic cell nuclear transfer (SCNT), and induced pluripotent stem cells (iPS) . And we will discuss effects of H3.3 incorporation into rDNA chromatin on rRNA transcription. Furthermore, we will try to improve reprogramming efficiency through regulate rRNA transcription by controling H3.3 incorportion. We believe this study will facilitate understanding of histone code and rDNA activity involving in somatic reprogramming, and will be of great significance to apply SCNT and iPS technologies into practice.
