Yoshida M, Horinouchi S, Beppu T
Department of Biotechnology, University of Tokyo, Japan.
Bioessays. 1995 May;17(5):423-30. doi: 10.1002/bies.950170510.
Reversible acetylation at the epsilon-amino group of lysines located at the conserved domain of core histones is supposed to play an important role in the regulation of chromatin structure and its transcriptional activity. One promising strategy for analyzing the precise function of histone acetylation is to block the activities of acetylating or deacetylating enzymes by specific inhibitors. Recently, two microbial metabolites, trichostatin A and trapoxin, were found to be potent inhibitors of histone deacetylases. Trichostatin A reversibly inhibits the mammalian histone deacetylase, whereas trapoxin causes inhibition through irreversible binding to the enzyme. The histone deacetylase from a trichostatin A-resistant cell line is resistant to trichostatin A, indicating that the enzyme is the primary target. Both of the agents induce a variety of biological responses of cells such as induction of differentiation and cell cycle arrest. Trichostatin A and trapoxin are useful in analyzing the role of histone acetylation in chromatin structure and function as well as in determining the genes whose activities are regulated by histone acetylation.
位于核心组蛋白保守结构域的赖氨酸ε-氨基上的可逆乙酰化，被认为在染色质结构及其转录活性的调节中起重要作用。分析组蛋白乙酰化精确功能的一种有前景的策略是通过特异性抑制剂阻断乙酰化或去乙酰化酶的活性。最近，发现两种微生物代谢产物曲古抑菌素A和 trapoxin 是组蛋白去乙酰化酶的有效抑制剂。曲古抑菌素A可逆地抑制哺乳动物组蛋白去乙酰化酶，而 trapoxin 通过与该酶不可逆结合导致抑制。来自曲古抑菌素A抗性细胞系的组蛋白去乙酰化酶对曲古抑菌素A具有抗性，表明该酶是主要靶点。这两种试剂都能诱导细胞的多种生物学反应，如诱导分化和细胞周期停滞。曲古抑菌素A和 trapoxin 可用于分析组蛋白乙酰化在染色质结构和功能中的作用，以及确定其活性受组蛋白乙酰化调节的基因。
