Backs Johannes, Olson Eric N
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Circ Res. 2006 Jan 6;98(1):15-24. doi: 10.1161/01.RES.0000197782.21444.8f.
Histones control gene expression by modulating the structure of chromatin and the accessibility of regulatory DNA sequences to transcriptional activators and repressors. Posttranslational modifications of histones have been proposed to establish a "code" that determines patterns of cellular gene expression. Acetylation of histones by histone acetyltransferases stimulates gene expression by relaxing chromatin structure, allowing access of transcription factors to DNA, whereas deacetylation of histones by histone deacetylases promotes chromatin condensation and transcriptional repression. Recent studies demonstrate histone acetylation/deacetylation to be a nodal point for the control of cardiac growth and gene expression in response to acute and chronic stress stimuli. These findings suggest novel strategies for "transcriptional therapies" to control cardiac gene expression and function. Manipulation of histone modifying enzymes and the signaling pathways that impinge on them in the settings of pathological cardiac growth, remodeling, and heart failure represents an auspicious therapeutic approach.
组蛋白通过调节染色质结构以及调控性DNA序列对转录激活因子和抑制因子的可及性来控制基因表达。有人提出组蛋白的翻译后修饰可建立一种“密码”，该密码决定细胞基因表达模式。组蛋白乙酰转移酶对组蛋白的乙酰化通过松弛染色质结构来刺激基因表达，使转录因子能够接触DNA，而组蛋白去乙酰化酶对组蛋白的去乙酰化则促进染色质浓缩和转录抑制。最近的研究表明，组蛋白乙酰化/去乙酰化是控制心脏生长以及响应急性和慢性应激刺激时基因表达的一个关键点。这些发现提示了用于“转录疗法”以控制心脏基因表达和功能的新策略。在病理性心脏生长、重塑和心力衰竭的情况下，操纵组蛋白修饰酶以及作用于它们的信号通路是一种有前景的治疗方法。
