Coordinating Regulation of Gene Expression in Cardiovascular Disease: Interactions between Chromatin Modifiers and Transcription Factors.
Coordinating Regulation of Gene Expression in Cardiovascular Disease: Interactions between Chromatin Modifiers and Transcription Factors.
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DOI：
10.3389/fcvm.2017.00019
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发表时间：
2017
影响因子：
3.6
通讯作者：
Martin KA
中科院分区：
文献类型：
--
作者：
Bauer AJ;Martin KA
心血管疾病是导致死亡的主要原因，并增加了经济负担。心血管疾病的发病机制很复杂，但可能由遗传和/或环境危险因素引起。这可能导致多种细胞类型的基因表达失调，包括心肌细胞、内皮细胞、血管平滑肌细胞和炎症细胞。虽然最初的研究涉及基因表达的转录控制，但人们越来越认识到表观遗传学通过改变染色质结构和基因可及性在这一过程中发挥着重要作用。染色质修饰蛋白（包括调节 DNA 甲基化、组蛋白甲基化和组蛋白乙酰化的酶）可以通过多种方式影响基因表达。这些染色质修饰剂及其标记可以通过对 DNA、组蛋白或转录因子本身的修饰来促进或阻止转录因子招募到基因调控区域。本综述将重点关注表观遗传修饰剂和转录因子如何相互作用以协调调节心血管疾病中的基因表达这一新出现的问题。虽然大多数研究已经解决了表观遗传或转录控制的作用，但我们对这些过程整合的理解才刚刚开始。探究这些相互作用具有挑战性，需要改进的技术方法来充分剖析心血管疾病中转录因子、染色质修饰剂和基因表达之间的时间和空间关系。我们总结了该领域的现状，并提供了有关局限性和未来方向的观点。通过表观遗传和转录相互作用的研究，我们可以加深对心血管疾病发病机制基本机制的理解，从而开发新的治疗方法。
Cardiovascular disease is a leading cause of death with increasing economic burden. The pathogenesis of cardiovascular diseases is complex, but can arise from genetic and/or environmental risk factors. This can lead to dysregulated gene expression in numerous cell types including cardiomyocytes, endothelial cells, vascular smooth muscle cells, and inflammatory cells. While initial studies addressed transcriptional control of gene expression, epigenetics has been increasingly appreciated to also play an important role in this process through alterations in chromatin structure and gene accessibility. Chromatin-modifying proteins including enzymes that modulate DNA methylation, histone methylation, and histone acetylation can influence gene expression in numerous ways. These chromatin modifiers and their marks can promote or prevent transcription factor recruitment to regulatory regions of genes through modifications to DNA, histones, or the transcription factors themselves. This review will focus on the emerging question of how epigenetic modifiers and transcription factors interact to coordinately regulate gene expression in cardiovascular disease. While most studies have addressed the roles of either epigenetic or transcriptional control, our understanding of the integration of these processes is only just beginning. Interrogating these interactions is challenging, and improved technical approaches will be needed to fully dissect the temporal and spatial relationships between transcription factors, chromatin modifiers, and gene expression in cardiovascular disease. We summarize the current state of the field and provide perspectives on limitations and future directions. Through studies of epigenetic and transcriptional interactions, we can advance our understanding of the basic mechanisms of cardiovascular disease pathogenesis to develop novel therapeutics.