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发育与疾病中的表观遗传记忆:机制解析。

Epigenetic memory in development and disease: Unraveling the mechanism.

机构信息

Department of Medicine (Biomedical Genetics Section and Cancer Center), Department of Pathology & Laboratory Medicine, Department of Pharmacology & Experimental Therapeutics, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, United States of America.

出版信息

Biochim Biophys Acta Rev Cancer. 2020 Apr;1873(2):188349. doi: 10.1016/j.bbcan.2020.188349. Epub 2020 Jan 23.

Abstract

Epigenetic memory is an essential process of life that governs the inheritance of predestined functional characteristics of normal cells and the newly acquired properties of cells affected by cancer and other diseases from parental to progeny cells. Unraveling the molecular basis of epigenetic memory dictated by protein and RNA factors in conjunction with epigenetic marks that are erased and re-established during embryogenesis/development during the formation of somatic, stem and disease cells will have far reaching implications to our understanding of embryogenesis/development and various diseases including cancer. While there has been enormous progress made, there are still gaps in knowledge which includes, the identity of unique epigenetic memory factors (EMFs) and epigenome coding enzymes/co-factors/scaffolding proteins involved in the assembly of defined "epigenetic memorysomes" and the epigenome marks that constitute collections of gene specific epigenetic memories corresponding to specific cell types and physiological conditions. A better understanding of the molecular basis for epigenetic memory will play a central role in improving diagnostics and prognostics of disease states and aid the development of targeted therapeutics of complex diseases.

摘要

表观遗传记忆是生命的一个基本过程,它控制着正常细胞预定功能特征的遗传,以及受癌症和其他疾病影响的细胞的新获得的特性从亲代细胞到子代细胞。揭示由蛋白质和 RNA 因子以及表观遗传标记共同决定的表观遗传记忆的分子基础,这些标记在胚胎发生/发育过程中被抹去和重新建立,对于我们理解胚胎发生/发育和各种疾病包括癌症具有深远的意义。尽管已经取得了巨大的进展,但仍存在知识上的差距,包括独特的表观遗传记忆因子(EMFs)的身份,以及参与组装特定“表观遗传记忆体”的表观基因组编码酶/共因子/支架蛋白,以及构成特定细胞类型和生理条件下基因特异性表观遗传记忆的集合的表观基因组标记。更好地理解表观遗传记忆的分子基础将在改善疾病状态的诊断和预后以及辅助复杂疾病的靶向治疗的发展中发挥核心作用。

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