Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Laboratory of Chromatin Biology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, India.
J Mol Biol. 2018 Sep 14;430(18 Pt B):3051-3067. doi: 10.1016/j.jmb.2018.07.013. Epub 2018 Jul 25.
Post-translational modifications (PTMs) of histone proteins play a crucial role in the regulation of chromatin structure and functions. Studies in the last few decades have revealed the significance of histone PTMs in key cellular processes including DNA replication, repair, transcription, apoptosis and cell cycle regulation. The PTMs on histones are carried out by chromatin modifiers, which are reversible in nature. The dynamic activity of chromatin modifiers maintains the levels of different PTMs on histones. The modified histones are recognized by reader proteins, which recruit effector proteins to regulate the function. The interplay between histone PTMs and chromatin dynamics plays a major role in the regulation of most of the cellular processes. Importantly, the perturbations in the histone PTMs by various intrinsic or extrinsic factors can cause defects in fundamental cellular processes leading to a wide range of diseases. The proteolytic clipping of histone proteins has also been shown to regulate many biological processes. Histone clipping has been observed from yeast to mammals, suggesting that this mechanism is a conserved epigenetic phenomenon. In this review, we have summarized the significance of histone clipping and provided future directions to comprehend the mechanism of this distinct and poorly understood epigenetic event.
组蛋白的翻译后修饰(PTMs)在调节染色质结构和功能中起着至关重要的作用。在过去几十年的研究中,人们揭示了组蛋白 PTM 在包括 DNA 复制、修复、转录、凋亡和细胞周期调控在内的关键细胞过程中的重要性。组蛋白上的 PTM 由染色质修饰物完成,这些修饰物本质上是可逆的。染色质修饰物的动态活性维持了组蛋白上不同 PTM 的水平。经过修饰的组蛋白被阅读器蛋白识别,这些阅读器蛋白招募效应蛋白来调节功能。组蛋白 PTM 和染色质动力学之间的相互作用在大多数细胞过程的调节中起着主要作用。重要的是,各种内在或外在因素对组蛋白 PTM 的干扰会导致基本细胞过程的缺陷,从而导致广泛的疾病。组蛋白蛋白的蛋白水解剪辑也被证明可以调节许多生物过程。从酵母到哺乳动物都观察到了组蛋白剪辑,这表明这种机制是一种保守的表观遗传现象。在这篇综述中,我们总结了组蛋白剪辑的意义,并为理解这一独特且了解甚少的表观遗传事件的机制提供了未来的方向。