From the Departments of Anesthesiology, Medicine, and Physiology, David Geffen School of Medicine, University of California, Los Angeles.
Circ Res. 2018 May 25;122(11):1586-1607. doi: 10.1161/CIRCRESAHA.118.311597.
If unifying principles could be revealed for how the same genome encodes different eukaryotic cells and for how genetic variability and environmental input are integrated to impact cardiovascular health, grand challenges in basic cell biology and translational medicine may succumb to experimental dissection. A rich body of work in model systems has implicated chromatin-modifying enzymes, DNA methylation, noncoding RNAs, and other transcriptome-shaping factors in adult health and in the development, progression, and mitigation of cardiovascular disease. Meanwhile, deployment of epigenomic tools, powered by next-generation sequencing technologies in cardiovascular models and human populations, has enabled description of epigenomic landscapes underpinning cellular function in the cardiovascular system. This essay aims to unpack the conceptual framework in which epigenomes are studied and to stimulate discussion on how principles of chromatin function may inform investigations of cardiovascular disease and the development of new therapies.
如果能够揭示出相同基因组如何编码不同的真核细胞,以及遗传变异和环境输入如何整合来影响心血管健康的统一原则,那么基础细胞生物学和转化医学中的重大挑战可能会屈服于实验分析。大量的模型系统研究表明,染色质修饰酶、DNA 甲基化、非编码 RNA 以及其他转录组塑造因子在成年健康以及心血管疾病的发展、进展和缓解中发挥着重要作用。与此同时,在心血管模型和人类群体中应用基于下一代测序技术的表观基因组学工具,已经能够描述心血管系统中细胞功能的表观基因组图谱。本文旨在剖析研究表观基因组的概念框架,并激发关于染色质功能原则如何为心血管疾病的研究和新疗法的开发提供信息的讨论。