Mann Derek A
Fibrosis Research Laboratories, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Hepatology. 2014 Oct;60(4):1418-25. doi: 10.1002/hep.27131. Epub 2014 May 7.
Epigenetics is a term that encompasses a variety of regulatory processes that are able to crosstalk in order to influence gene expression and cell phenotype in response to environmental cues. A deep understanding of epigenetics offers the potential for fresh insights into the basis for complex chronic diseases and improved diagnostic and prognostic tools. Moreover, as epigenetic modifications are highly plastic and responsive to the environment, there is much excitement around the theme of epigenetic therapeutics, including not only new drugs but also more informed patient advice on lifestyle choices and their impact on pathology. This review briefly explains the molecular nature of the individual regulatory process that constitute epigenetics, including DNA methylation, histone modifications, chromatin remodeling, transcriptional control, and noncoding RNAs. The ways in which these epigenetic mechanisms influence liver physiology and disease will be considered in detail, particularly in the context of cancer, fibrosis, and nonalcoholic steatohepatitis. The current limitations associated with epigenetic profiling and therapeutics in liver disease are discussed, as is the intriguing possibility that environmental-induced epigenetic changes may become stable and heritable.
The aim of the review is to inform hepatologists of the emerging key epigenetic ideas of relevance to liver diseases that are highly likely to form a component of patient management and care in the next decade.
表观遗传学是一个涵盖多种调控过程的术语，这些调控过程能够相互作用，以响应环境线索影响基因表达和细胞表型。深入了解表观遗传学有望为复杂慢性疾病的发病基础提供新的见解，并改进诊断和预后工具。此外，由于表观遗传修饰具有高度可塑性且对环境有反应，围绕表观遗传治疗的主题有很多令人兴奋的地方，这不仅包括新药，还包括关于生活方式选择及其对病理影响的更明智的患者建议。本综述简要解释了构成表观遗传学的各个调控过程的分子本质，包括DNA甲基化、组蛋白修饰、染色质重塑、转录调控和非编码RNA。将详细探讨这些表观遗传机制影响肝脏生理和疾病的方式，特别是在癌症、纤维化和非酒精性脂肪性肝炎的背景下。讨论了目前与肝脏疾病表观遗传分析和治疗相关的局限性，以及环境诱导的表观遗传变化可能变得稳定且可遗传的有趣可能性。
本综述的目的是让肝病学家了解与肝脏疾病相关的新兴关键表观遗传学观点，这些观点极有可能在未来十年成为患者管理和护理的一部分。
