Smith Catharine L
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, 1703 E. Mabel St, Tucson, AZ 85721, USA.
Bioessays. 2008 Jan;30(1):15-24. doi: 10.1002/bies.20687.
Transcriptional repression and silencing have been strongly associated with hypoacetylation of histones. Accordingly, histone deacetylases, which remove acetyl groups from histones, have been shown to participate in mechanisms of transcriptional repression. Therefore, current models of the role of acetylation in transcriptional regulation focus on the acetylation status of histones and designate histone acetyltransferases, which add acetyl groups to histones, as transcriptional coactivators and histone deacetylases as corepressors. In recent years, an accumulation of studies have shown that these enzymes also target non-histone proteins and that histone deacetylases have clear roles as coactivators at a variety of genes, some of which are key regulators of cell growth and survival. This review summarizes the evidence for histone deacetylases as coactivators and provides models of coactivation mechanisms, some of which integrate roles of acetylated histones and non-histone proteins in transcription.
转录抑制和基因沉默与组蛋白低乙酰化密切相关。因此，能从组蛋白上去除乙酰基的组蛋白脱乙酰酶已被证明参与转录抑制机制。所以，目前关于乙酰化在转录调控中作用的模型聚焦于组蛋白的乙酰化状态，并将向组蛋白添加乙酰基的组蛋白乙酰转移酶指定为转录共激活因子，而将组蛋白脱乙酰酶指定为共抑制因子。近年来，大量研究表明这些酶也作用于非组蛋白，并且组蛋白脱乙酰酶在多种基因中作为共激活因子发挥着明确作用，其中一些基因是细胞生长和存活的关键调节因子。本综述总结了组蛋白脱乙酰酶作为共激活因子的证据，并提供了共激活机制模型，其中一些模型整合了乙酰化组蛋白和非组蛋白在转录中的作用。
