Niemann Heiner, Tian X Cindy, King W Allan, Lee Rita S F
Department of Biotechnology, Institute for Animal Breeding (FAL), Mariensee, Hoeltystr. 10, 31535 Neustadt, Germany .
Reproduction. 2008 Feb;135(2):151-63. doi: 10.1530/REP-07-0397.
The birth of 'Dolly', the first mammal cloned from an adult donor cell, has sparked a flurry of research activities to improve cloning technology and to understand the underlying mechanism of epigenetic reprogramming of the transferred somatic cell nucleus. Especially in ruminants, somatic cell nuclear transfer (SCNT) is frequently associated with pathological changes in the foetal and placental phenotype and has significant consequences for development both before and after birth. The most critical factor is epigenetic reprogramming of the transferred somatic cell nucleus from its differentiated status into the totipotent state of the early embryo. This involves an erasure of the gene expression program of the respective donor cell and the establishment of the well-orchestrated sequence of expression of an estimated number of 10 000-12 000 genes regulating embryonic and foetal development. The following article reviews the present knowledge on the epigenetic reprogramming of the transferred somatic cell nucleus, with emphasis on DNA methylation, imprinting, X-chromosome inactivation and telomere length restoration in bovine development. Additionally, we briefly discuss other approaches towards epigenetic nuclear reprogramming, including the fusion of somatic and embryonic stem cells and the overexpression of genes crucial in the formation and maintenance of the pluripotent status. Improvements in our understanding of this dramatic epigenetic reprogramming event will be instrumental in realising the great potential of SCNT for basic biological research and for various agricultural and biomedical applications.
“多莉”是第一只从成年供体细胞克隆而来的哺乳动物，它的诞生引发了一系列研究活动，旨在改进克隆技术，并了解转移的体细胞核表观遗传重编程的潜在机制。特别是在反刍动物中，体细胞核移植（SCNT）常常与胎儿和胎盘表型的病理变化相关联，对出生前后的发育都有重大影响。最关键的因素是将转移的体细胞核从其分化状态重编程为早期胚胎的全能状态。这涉及消除相应供体细胞的基因表达程序，并建立一个精心编排的、估计数量为10000 - 12000个调节胚胎和胎儿发育的基因的表达序列。以下文章综述了目前关于转移的体细胞核表观遗传重编程的知识，重点关注牛发育过程中的DNA甲基化、印记、X染色体失活和端粒长度恢复。此外，我们简要讨论了表观遗传核重编程的其他方法，包括体干细胞与胚胎干细胞的融合以及对多能状态形成和维持至关重要的基因的过表达。增进我们对这一显著的表观遗传重编程事件的理解，将有助于实现体细胞核移植在基础生物学研究以及各种农业和生物医学应用方面的巨大潜力。
