Vinken Mathieu, De Rop Evelien, Decrock Elke, De Vuyst Elke, Leybaert Luc, Vanhaecke Tamara, Rogiers Vera
Department of Toxicology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
Biochim Biophys Acta. 2009 Jan;1795(1):53-61. doi: 10.1016/j.bbcan.2008.08.002. Epub 2008 Aug 29.
The establishment of gap junctional intercellular communication is a prerequisite for appropriate control of tissue homeostasis. Gap junctions consist of connexin proteins, whereby a myriad of factors govern the connexin life cycle. At the transcriptional level, most attention has yet been paid to the classical cis/trans machinery (i.e. the interaction between transcription factors and regulatory elements in connexin gene promoter regions) as a gatekeeper of connexin expression. In the last few years, it has become clear that epigenetic processes are also essentially involved in connexin gene transcription. Major determinants of the epigenome include histone modifications and DNA methylation, and recently, microRNA species have also been described as key regulators of the epigenetic machinery. In the present paper, the emerging roles of epigenetic events in the control of connexin expression, and consequently of gap junctional intercellular communication, are reviewed. Besides an updated theoretical background concerning gap junctions and epigenetic phenomena, we provide an in-depth overview of their interrelationship and we demonstrate the clinical relevance of the topic.
间隙连接细胞间通讯的建立是适当控制组织稳态的前提条件。间隙连接由连接蛋白组成，众多因素调控着连接蛋白的生命周期。在转录水平上，作为连接蛋白表达的守门人，经典的顺式/反式机制（即转录因子与连接蛋白基因启动子区域调控元件之间的相互作用）受到了最多关注。在过去几年中，越来越清楚的是，表观遗传过程也在本质上参与了连接蛋白基因转录。表观基因组的主要决定因素包括组蛋白修饰和DNA甲基化，最近，微小RNA也被描述为表观遗传机制的关键调节因子。在本文中，我们综述了表观遗传事件在连接蛋白表达控制以及间隙连接细胞间通讯控制中新兴的作用。除了关于间隙连接和表观遗传现象的最新理论背景外，我们还深入概述了它们之间的相互关系，并展示了该主题的临床相关性。
