Thurston A, Lucas E S, Allegrucci C, Steele W, Young L E
Wolfson Centre for Stem cells, Tissue Engineering and Modelling (STEM), University of Nottingham, Centre for Biomolecular Sciences, University Park, Nottingham NG7 2RD, UK.
Theriogenology. 2007 Sep 1;68 Suppl 1:S98-106. doi: 10.1016/j.theriogenology.2007.03.020. Epub 2007 May 4.
It has been long known that the unique genetic sequence each embryo inherits is not the sole determinant of phenotype. However, only recently have epigenetic modifications to DNA been implicated in providing potential developmental plasticity to the embryonic and fetal genome, with environmental influences directly altering the epigenetic modifications that contribute to tissue-specific gene regulation. Most is known about the potential environmental regulation of DNA methylation, epigenetic addition of methyl groups to cytosine residues in DNA that acts in the long-term silencing of affected sequences. While most attention has been paid to the methylation of imprinted gene sequences, in terms of developmental plasticity there are many more parts of the genome that are methylated and that could be affected. This review explores the distribution of cytosine methylation in the genome and discusses the potential effects of regional plasticity on subsequent development. Widening our consideration of potentially plastic regions is likely to greatly enhance our understanding of how individuals are shaped not only by DNA sequence, but by the environment in which pluripotent embryonic cells are transformed into the many cell types of the body.
长期以来，人们都知道每个胚胎所继承的独特基因序列并非表型的唯一决定因素。然而，直到最近，DNA的表观遗传修饰才被认为在赋予胚胎和胎儿基因组潜在发育可塑性方面发挥作用，环境影响会直接改变有助于组织特异性基因调控的表观遗传修饰。关于DNA甲基化的潜在环境调控了解最多，DNA甲基化是指在DNA的胞嘧啶残基上表观遗传地添加甲基基团，其作用是长期沉默受影响的序列。虽然大多数注意力都集中在印记基因序列的甲基化上，但就发育可塑性而言，基因组中还有更多区域发生甲基化且可能受到影响。本文综述探讨了基因组中胞嘧啶甲基化的分布，并讨论了区域可塑性对后续发育的潜在影响。拓宽我们对潜在可塑性区域的思考，可能会极大地增进我们对个体如何不仅由DNA序列，而且由多能胚胎细胞转变为身体多种细胞类型的环境所塑造的理解。
