Trievel Raymond C
University of Michigan Medical School, Department of Biological Chemistry, Ann Arbor, MI 48109-0606, USA.
Crit Rev Eukaryot Gene Expr. 2004;14(3):147-69. doi: 10.1615/critreveukaryotgeneexpr.v14.i3.10.
Histones are the major protein constituent of chromatin in the eukaryotic nucleus. These proteins undergo a host of different post-translational modifications, including phosphorylation, acetylation, and methylation, which have profound effects on the remodeling of chromatin. Histone modifications can function either individually or combinatorially to govern such processes as transcription, replication, DNA repair, and apoptosis. Recent studies have focused on histone arginine and lysine methylation and the roles of these modifications in transcriptional regulation and the establishment of heterochromatin. Concomitantly, several families of histone methyltransferases (HMTs) have been identified that catalyze the methylation of specific arginines or lysines in histones H3 and H4. Not surprisingly, many of these methyltransferase genes had been previously identified as important genetic regulators in organisms such as yeast and Drosophila, which underscores the importance of histone methylation in transcriptional control and chromatin remodeling. Structures of several representatives of these HMT families have recently been determined, yielding insight into their catalytic mechanism and histone substrate specificity. The focus of this review is to briefly summarize the roles of histone methylation in chromatin remodeling and to discuss the structures, substrate specificities, and mechanisms of the different classes of HMTs.
组蛋白是真核细胞核中染色质的主要蛋白质成分。这些蛋白质会经历许多不同的翻译后修饰,包括磷酸化、乙酰化和甲基化,这些修饰对染色质重塑有深远影响。组蛋白修饰可以单独发挥作用,也可以组合起来调控转录、复制、DNA修复和细胞凋亡等过程。最近的研究集中在组蛋白精氨酸和赖氨酸甲基化以及这些修饰在转录调控和异染色质形成中的作用。与此同时,已经鉴定出几个组蛋白甲基转移酶(HMT)家族,它们催化组蛋白H3和H4中特定精氨酸或赖氨酸的甲基化。不出所料,这些甲基转移酶基因中的许多先前已被确定为酵母和果蝇等生物体中的重要遗传调节因子,这突出了组蛋白甲基化在转录控制和染色质重塑中的重要性。最近已经确定了这些HMT家族中几个代表的结构,从而深入了解了它们的催化机制和组蛋白底物特异性。本综述的重点是简要总结组蛋白甲基化在染色质重塑中的作用,并讨论不同类型HMT的结构、底物特异性和机制。