人类疾病中的表观遗传学及表观遗传治疗前景。

Epigenetics in human disease and prospects for epigenetic therapy.

作者信息

Egger Gerda, Liang Gangning, Aparicio Ana, Jones Peter A

机构信息

Department of Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, 1441 Eastlake Avenue, Room 8302L, Los Angeles, California 90089-9181, USA.

出版信息

Nature. 2004 May 27;429(6990):457-63. doi: 10.1038/nature02625.

DOI:10.1038/nature02625

PMID:15164071

Abstract

Epigenetic mechanisms, which involve DNA and histone modifications, result in the heritable silencing of genes without a change in their coding sequence. The study of human disease has focused on genetic mechanisms, but disruption of the balance of epigenetic networks can cause several major pathologies, including cancer, syndromes involving chromosomal instabilities, and mental retardation. The development of new diagnostic tools might reveal other diseases that are caused by epigenetic alterations. Great potential lies in the development of 'epigenetic therapies'--several inhibitors of enzymes controlling epigenetic modifications, specifically DNA methyltransferases and histone deacetylases, have shown promising anti-tumorigenic effects for some malignancies.

摘要

表观遗传机制涉及DNA和组蛋白修饰，可导致基因的可遗传沉默，而其编码序列不发生改变。人类疾病研究主要集中在遗传机制上，但表观遗传网络平衡的破坏会引发多种重大疾病，包括癌症、涉及染色体不稳定的综合征以及智力迟钝。新诊断工具的开发可能会揭示其他由表观遗传改变引起的疾病。“表观遗传疗法”的发展具有巨大潜力——几种控制表观遗传修饰的酶的抑制剂，特别是DNA甲基转移酶和组蛋白脱乙酰酶抑制剂，对某些恶性肿瘤已显示出有前景的抗肿瘤作用。