Choi Jennifer K, Howe Leann J
Department of Biochemistry and Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BCV6T1Z3, Canada.
Biochem Cell Biol. 2009 Feb;87(1):139-50. doi: 10.1139/O08-112.
Eukaryotic DNA is packaged into a nucleoprotein structure known as chromatin, which is comprised of DNA, histones, and nonhistone proteins. Chromatin structure is highly dynamic, and can shift from a transcriptionally inactive state to an active form in response to intra- and extracellular signals. A major factor in chromatin architecture is the covalent modification of histones through the addition of chemical moieties, such as acetyl, methyl, ubiquitin, and phosphate groups. The acetylation of the amino-terminal tails of histones is a process that is highly conserved in eukaryotes, and was one of the earliest histone modifications characterized. Since its identification in 1964, a large body of evidence has accumulated demonstrating that histone acetylation plays an important role in transcription. Despite our ever-growing understanding of the nuclear processes involved in nucleosome acetylation, however, the exact biochemical mechanisms underlying the downstream effects of histone acetylation have yet to be fully elucidated. To date, histone acetylation has been proposed to function in 2 nonmutually exclusive manners: by directly altering chromatin structure, and by acting as a molecular tag for the recruitment of chromatin-modifying complexes. Here, we discuss recent research focusing on these 2 potential roles of histone acetylation and clarify what we actually know about the function of this modification.
真核生物的DNA被包装成一种称为染色质的核蛋白结构,它由DNA、组蛋白和非组蛋白组成。染色质结构具有高度动态性,能够响应细胞内和细胞外信号,从转录无活性状态转变为活性形式。染色质结构的一个主要因素是通过添加化学基团(如乙酰基、甲基、泛素和磷酸基团)对组蛋白进行共价修饰。组蛋白氨基末端尾巴的乙酰化是真核生物中高度保守的过程,也是最早被表征的组蛋白修饰之一。自1964年被发现以来,大量证据积累表明组蛋白乙酰化在转录中起重要作用。然而,尽管我们对参与核小体乙酰化的核过程的理解不断加深,但组蛋白乙酰化下游效应的确切生化机制尚未完全阐明。迄今为止,组蛋白乙酰化被认为以两种并非相互排斥的方式发挥作用:通过直接改变染色质结构,以及作为招募染色质修饰复合物的分子标签。在这里,我们讨论了聚焦于组蛋白乙酰化这两种潜在作用的最新研究,并阐明了我们对这种修饰功能的实际了解。