University of Lille 1, Unité de Glycobiologie Structurale et Fonctionnelle, CNRS UMR8576, Lille, France.
Institute Lorentz for Theoretical Physics, Leiden University, Leiden, the Netherlands.
Biophys J. 2018 May 22;114(10):2255-2261. doi: 10.1016/j.bpj.2017.12.008. Epub 2018 Jan 6.
In its most restrictive interpretation, the notion of chromatin remodeling refers to the action of chromatin-remodeling enzymes on nucleosomes with the aim of displacing and removing them from the chromatin fiber (the effective polymer formed by a DNA molecule and proteins). This local modification of the fiber structure can have consequences for the initiation and repression of the transcription process, and when the remodeling process spreads along the fiber, it also results in long-range effects essential for fiber condensation. There are three regulatory levels of relevance that can be distinguished for this process: the intrinsic sequence preference of the histone octamer, which rules the positioning of the nucleosome along the DNA, notably in relation to the genetic information coded in DNA; the recognition or selection of nucleosomal substrates by remodeling complexes; and, finally, the motor action on the nucleosome exerted by the chromatin remodeler. Recent work has been able to provide crucial insights at each of these three levels that add new twists to this exciting and unfinished story, which we highlight in this perspective.
在其最严格的解释中,染色质重塑的概念是指染色质重塑酶对核小体的作用,目的是将其从染色质纤维(由 DNA 分子和蛋白质形成的有效聚合物)中置换和去除。这种纤维结构的局部修饰可能会影响转录过程的起始和抑制,而当重塑过程沿着纤维扩散时,它还会导致对纤维浓缩至关重要的长程效应。对于这个过程,可以区分三个相关的调节水平:组蛋白八聚体的固有序列偏好,它决定了核小体在 DNA 上的定位,特别是与 DNA 中编码的遗传信息有关;重塑复合物对核小体底物的识别或选择;最后,染色质重塑剂对核小体的马达作用。最近的工作能够在这三个水平中的每一个水平上提供关键的见解,为这个令人兴奋但尚未完成的故事增添了新的曲折,我们在这篇观点文章中强调了这一点。