School of Life and Environmental Sciences, University of Sydney, Darlington, NSW 2006, Australia.
Biochem Soc Trans. 2024 Oct 30;52(5):1995-2008. doi: 10.1042/BST20230070.
Chromatin remodelling enzymes reposition nucleosomes throughout the genome to regulate the rate of transcription and other processes. These enzymes have been studied intensively since the 1990s, and yet the mechanism by which they operate has only very recently come into focus, following advances in cryoelectron microscopy and single-molecule biophysics. CHD4 is an essential and ubiquitous chromatin remodelling enzyme that until recently has received less attention than remodellers such as Snf2 and CHD1. Here we review what recent work in the field has taught us about how CHD4 reshapes the genome. Cryoelectron microscopy and single-molecule studies demonstrate that CHD4 shares a central remodelling mechanism with most other chromatin remodellers. At the same time, differences between CHD4 and other chromatin remodellers result from the actions of auxiliary domains that regulate remodeller activity by for example: (1) making differential interactions with nucleosomal epitopes such as the acidic patch and the N-terminal tail of histone H4, and (2) inducing the formation of distinct multi-protein remodelling complexes (e.g. NuRD vs ChAHP). Thus, although we have learned much about remodeller activity, there is still clearly much more waiting to be revealed.
染色质重塑酶在整个基因组中重新定位核小体,以调节转录和其他过程的速率。自 20 世纪 90 年代以来,这些酶一直受到深入研究,但在冷冻电子显微镜和单分子生物物理学的进展之后,它们的作用机制最近才成为焦点。CHD4 是一种必需且普遍存在的染色质重塑酶,直到最近,它的关注度一直低于 Snf2 和 CHD1 等重塑酶。在这里,我们回顾了该领域最近的工作,了解了 CHD4 如何重塑基因组。冷冻电子显微镜和单分子研究表明,CHD4 与大多数其他染色质重塑酶共享一个核心重塑机制。与此同时,CHD4 和其他染色质重塑酶之间的差异源于辅助结构域的作用,这些结构域通过例如以下方式调节重塑酶的活性:(1)与核小体表位(如酸性斑和组蛋白 H4 的 N 端尾巴)进行差异相互作用,以及 (2)诱导形成不同的多蛋白重塑复合物(例如 NuRD 与 ChAHP)。因此,尽管我们已经了解了很多关于重塑酶活性的知识,但显然还有更多的知识等待我们去揭示。