Insights into the role of DNA methylation in disease through the use of mouse models
Insights into the role of DNA methylation in disease through the use of mouse models
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DOI：
10.1242/dmm.004812
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发表时间：
2010-05-01
影响因子：
4.3
通讯作者：
Grady, William M.
中科院分区：
文献类型：
--
作者：
Conerly, Melissa;Grady, William M.
表观遗传学最初被定义为基因与其环境的相互作用，从而产生表型。现在它指的是在 DNA 序列不发生变化的情况下发生的基因表达的可遗传变化的研究。迄今为止，最了解的表观遗传机制是 CpG DNA 甲基化和组蛋白修饰。 DNA 甲基化尤其引起了人们的强烈兴趣，因为它最近在疾病以及生物体的发育和正常功能中发挥着重要作用。疾病相关研究的大部分焦点都集中在癌症上，因为人们认识到表观遗传改变在癌症中很常见，并且可能与遗传改变共同促进癌症的形成。我们对控制基因表达的表观遗传机制的理解源于对细胞系系统和简单模型系统（例如拟南芥）的研究。我们现在正在进入一个更复杂的模型系统时代，例如转基因和基因敲除小鼠模型，这将导致我们进一步深入了解发育和人类疾病中的表观遗传学。目前的模型揭示了表观遗传机制的复杂的、组织特异性的影响，并进一步让我们了解 DNA 甲基化和组蛋白修饰对疾病和发育的作用。这些模型的当前状态是本评论的主题。
Epigenetics was originally defined as the interaction of genes with their environment that brings the phenotype into being. It now refers to the study of heritable changes in gene expression that occur without a change in DNA sequence. To date, the best understood epigenetic mechanisms are CpG DNA methylation and histone modifications. DNA methylation in particular has been the subject of intense interest because of its recently recognized role in disease, as well as in the development and normal function of organisms. Much of the focus of disease-related research has been on cancer because of the recognition that epigenetic alterations are common in cancer and probably cooperate with genetic alterations to drive cancer formation. Our understanding of epigenetic mechanisms in controlling gene expression has resulted from the study of cell line systems and simple model systems, such as Arabidopsis thaliana. We are now moving into an era of more complex model systems, such as transgenic and knockout mouse models, which will lead to further insight into epigenetics in development and human disease. The current models have revealed complex, tissue-specific effects of epigenetic mechanisms and have further informed our understanding of the role of DNA methylation and histone modifications on disease and development. The current state of these models is the subject of this Commentary.