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哺乳动物表观基因组学:为发育与治疗对基因组进行重编程

Mammalian epigenomics: reprogramming the genome for development and therapy.

作者信息

Reik W, Santos F, Dean W

机构信息

Laboratory of Developmental Genetics and Imprinting, Developmental Genetics Programme, The Babraham Institute, Cambridge CB2 4AT, UK.

出版信息

Theriogenology. 2003 Jan 1;59(1):21-32. doi: 10.1016/s0093-691x(02)01269-4.

DOI:10.1016/s0093-691x(02)01269-4
PMID:12499015
Abstract

Epigenetic modifications of DNA and chromatin are important for genome function during development and in adults. DNA and chromatin modifications have central importance for genomic imprinting and other aspects of epigenetic control of gene expression. In somatic lineages, modifications are generally stably maintained and are characteristic of different specialized tissues. The mammalian genome undergoes major reprogramming of modification patterns in germ cells and in the early embryo. Some of the factors that are involved both in maintenance and in reprogramming, such as methyltransferases, are being identified. Epigenetic reprogramming is deficient in animal cloning, which is a major explanation for the inefficiency of the cloning procedure. Deficiencies in reprogramming are likely to underlie the occurrence of epimutations and of epigenetic inheritance. Environmental factors can alter epigenetic modifications and may thus have long-lasting effects on phenotype. Epigenomics methods are being developed to catalogue genome modifications under normal and pathological conditions. Epigenetic engineering is likely to play an important role in medicine in the future.

摘要

DNA和染色质的表观遗传修饰对于发育过程中和成体中的基因组功能至关重要。DNA和染色质修饰对于基因组印记以及基因表达表观遗传控制的其他方面具有核心重要性。在体细胞谱系中,修饰通常稳定维持,并且是不同专门组织的特征。哺乳动物基因组在生殖细胞和早期胚胎中经历修饰模式的重大重编程。一些参与维持和重编程的因子,如甲基转移酶,正在被识别。表观遗传重编程在动物克隆中存在缺陷,这是克隆程序效率低下的主要原因。重编程缺陷可能是表型突变和表观遗传遗传发生的基础。环境因素可改变表观遗传修饰,因此可能对表型产生持久影响。表观基因组学方法正在被开发以编目正常和病理条件下的基因组修饰。表观遗传工程未来可能在医学中发挥重要作用。

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