Epigenetics in disease: Leader or follower?
Epigenetics in disease: Leader or follower?
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DOI：
10.4161/epi.6.7.16498
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发表时间：
2011-07
期刊：
影响因子：
3.7
通讯作者：
David I. K. Martin;Jennifer E. Cropley;C. Suter
中科院分区：
文献类型：
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作者：
David I. K. Martin;Jennifer E. Cropley;C. Suter
表观遗传沉默是多细胞真核生物中普遍存在的基因调控模式：体细胞类型的稳定分化需要维持处于活性或沉默状态的基因子集。所涉及的分子的多样性，以及对表观遗传状态的主动维持的要求，产生了大规模错误的可能性。当表观遗传错误或表观突变激活或破坏一个关键基因时，它们可能导致疾病。发生在生殖系或早期胚胎中的表突变可影响全部或大部分索马和表型遗传病。但表观遗传现象的随机性和可逆性预示着表观突变可能是镶嵌的，并以非孟德尔方式遗传;因此，表观遗传疾病很少会以遗传疾病的可轻松预测的方式表现，而是会表现出可变的表现力和复杂的遗传模式。许多表型变异和常见疾病可以用表观遗传变异和畸变来解释。目前已知的真正表观遗传疾病的例子是有限的，但这可能只是反映了区分因果表观遗传畸变与那些仅仅是疾病后果的困难，环境因素对表观遗传机制的影响进一步扩大了这一挑战。表观基因组的快速发展的分子表征，以及在整个基因组上调查表观遗传标记的新能力，可能会回答关于表观遗传学在疾病中的因果作用的许多问题;这些答案有可能改变我们对人类疾病的理解。
Epigenetic silencing is a pervasive mode of gene regulation in multicellular eukaryotes: stable differentiation of somatic cell types requires the maintenance of subsets of genes in an active or silent state. The variety of molecules involved, and the requirement for active maintenance of epigenetic states, creates the potential for errors on a large scale. When epigenetic errors - or epimutations - activate or inactivate a critical gene, they may cause disease. An epimutation that occurs in the germline or early embryo can affect all, or most, of the soma and phenocopy genetic disease. But the stochastic and reversible nature of epigenetic phenomena predicts that epimutations are likely to be mosaic and inherited in a nonmendelian manner; epigenetic diseases will thus rarely behave in the comfortably predictable manner of genetic diseases but will display variable expressivity and complex patterns of inheritance. Much phenotypic variation and common disease might be explained by epigenetic variation and aberration. The known examples of true epigenetic disease are at present limited, but this may reflect only the difficulty in distinguishing causal epigenetic aberrations from those that are merely consequences of disease, a challenge further extended by the impact of environmental agents on epigenetic mechanisms. The rapidly developing molecular characterization of epigenomes, and the new ability to survey epigenetic marks on whole genomes, may answer many questions about the causal role of epigenetics in disease; these answers have the potential to transform our understanding of human disease.