副突变及其表观遗传机制的研究进展  

Advances of Epigenetic Studies on Mechanisms of Paramutation

作　　者：程杉[1] 王晓荣[1] 丁卫[1] 

机构地区：[1]首都医科大学基础医学院生物化学与分子生物学系,北京100069

出　　处：《生理科学进展》2016年第1期7-13,共7页Progress in Physiological Sciences

基　　金：国家自然科学基金(81201816);北京市教委科技发展计划(KM201310025003)资助课题

摘　　要：经典遗传学的研究方法为许多遗传性疾病和遗传相关性疾病的预防、诊断和治疗提供了在分子水平上的直接线索,然而人类疾病的遗传表现始终存在着经典遗传学法则所不能解释的现象。副突变(paramutation)是上世纪50年代首次在玉米中发现的一种非孟氏遗传模式,其传递的等位基因不存在核苷酸序列的差异,提示了表观遗传机制可能参与了基因表达和表型的可遗传变化。近期的研究发现关于副突变现象的解释可能涉及一种新的表观遗传学调控机制,即由RNA(特别是非编码RNA)引发的基因组改变参与了副突变的发生和维持。其中DNA甲基转移酶II所介导的RNA甲基化发挥了极其重要的作用。对副突变及其机制的研究不仅能够深化人类对遗传和生命本质的认识,还有助于开拓在生物工程和疾病诊疗等应用领域的新思路。本文综述了副突变的分子机制和研究进展,并且探讨了副突变在疾病研究和基因治疗中的应用前景。Studies in traditional genetics have revealed the molecular causes of many genetic diseases and provided direct clues for their prevention, diagnosis and treatments, as well as for various disorders with genetic background. However, the genetic profiles of most human diseases could not be fully ex- plained with the canonical laws of genetics. Paramutation is one of non-Mendelian inheritance phenome- non, which was found in maize first in 1950s. The absence of alteration in nucleotide sequences in the gene-coding alleles suggested that paramutations might involve epigenetic mechanisms to transmit herita- ble changes in gene expression and determination of phenotypes. Recently, a novel epigenetic mechanism has been found in paramutation researches, emphasized the importance of DNA methyltransferase II medi- ated RNA （primarily non-coding RNAs） methylation in the occurrence and maintenance of paramuta- tions. Researches on paramutations and their epigenetic mechnisms will not only expand our understand- ing in the genetic principles of life, but also help ments. The present article reviewed the research h to develop new ideas for bioengineer and disease treat- ighlights on molecular mechanisms of paramutation discussed the prospects in disease study and therapy.

关 键 词：副突变 表观遗传学 非孟氏遗传 重复序列 DNA甲基转移酶 

分 类 号：R394[医药卫生—医学遗传学]