Ruzicka W Brad
From Harvard Medical and McLean Hospital, Belmont, MA.
Harv Rev Psychiatry. 2015 May-Jun;23(3):212-22. doi: 10.1097/HRP.0000000000000048.
Epigenetics is the study of chromatin-the physical material that forms chromosomes, composed of DNA wound around specialized histone proteins-and of how the modification of chromatin acts to establish stable states of gene expression in a cell-specific manner. Chromatin is regulated through three mechanisms: DNA methylation, histone modification, and RNA interference. These basic biological processes form the molecular interface between the genome and the environment, contributing to the regulation of gene expression in health and disease. Investigation of epigenetic mechanisms is yielding exciting insights in many areas of medicine, and a large and rapidly growing literature describes epigenetics as central to many aspects of the pathophysiology of psychotic disorders. This article first discusses speculative points as to why the mechanisms of epigenetics may be satisfying explanatory mechanisms in the etiology of psychotic disorders, then details emerging experimental evidence of roles for the three types of epigenetic mechanisms in these illnesses, and finally discusses these mechanisms as potentially compelling areas of research for the development of future treatments.
表观遗传学是对染色质(构成染色体的物理物质,由缠绕在特殊组蛋白上的DNA组成)以及染色质修饰如何以细胞特异性方式建立稳定的基因表达状态的研究。染色质通过三种机制进行调控:DNA甲基化、组蛋白修饰和RNA干扰。这些基本生物学过程构成了基因组与环境之间的分子界面,有助于健康和疾病状态下的基因表达调控。对表观遗传机制的研究在医学的许多领域都产生了令人兴奋的见解,并且大量且迅速增长的文献将表观遗传学描述为精神障碍病理生理学许多方面的核心。本文首先讨论关于表观遗传机制为何可能是精神障碍病因中令人满意的解释机制的推测性观点,然后详细阐述这三种表观遗传机制在这些疾病中作用的新出现的实验证据,最后讨论这些机制作为未来治疗开发潜在引人注目的研究领域。