Choo Kong-Bung
Faculty of Medicine and Health Sciences, University Tunku Abdul Rahman, Selangor, Malaysia.
Malays J Pathol. 2011 Dec;33(2):61-70.
Since the discovery of the double-helical structure of DNA, genetic regulation of gene expression has been well elucidated. More recently, another equally, if not more, important scheme of regulation of gene expression, called epigenetics, has emerged to explain the many biological observations that traditional genetic mechanisms have failed to decipher. Epigenetics is a discipline of study on the biological consequences of cellular alterations that do not involve nucleotide changes, as opposed to genetic mutations. Epigenetic changes are reversible and may lead to loss or gain of biological functions. The three most reported mechanisms of epigenetic regulation of gene expression involve changes in: (i) chromatin remodelling, (ii) DNA methylation and (iii) microRNA (miRNA). More importantly, many of the elucidated epigenetic changes are linked to the pathogenesis of human diseases and cancers. In this mini review, core concepts and basic experimental approaches in the study of epigenetic regulation of gene expression are briefly reviewed in relation to disease, with emphasis on cancer. This mini review also intends to highlight the fact that, besides genetics, epigenetics is now a discipline physicians and clinical research scientists can no longer ignore in their pursuit to understand disease and cancer and to develop new therapeutic strategies for treatment.
自DNA双螺旋结构被发现以来,基因表达的遗传调控已得到充分阐明。最近,另一种同样重要(甚至可能更重要)的基因表达调控机制——表观遗传学出现了,用以解释许多传统遗传机制无法破解的生物学现象。表观遗传学是一门研究不涉及核苷酸变化的细胞改变所产生的生物学后果的学科,与基因突变相对。表观遗传变化是可逆的,可能导致生物学功能的丧失或获得。基因表达表观遗传调控最常报道的三种机制涉及:(i)染色质重塑,(ii)DNA甲基化,以及(iii)微小RNA(miRNA)。更重要的是,许多已阐明的表观遗传变化与人类疾病和癌症的发病机制有关。在这篇小型综述中,结合疾病,简要回顾了基因表达表观遗传调控研究中的核心概念和基本实验方法,重点是癌症。这篇小型综述还旨在强调这样一个事实,即除了遗传学之外,表观遗传学现在已成为医生和临床研究科学家在试图理解疾病和癌症以及开发新的治疗策略时不能再忽视的一门学科。