自然杂志 ›› 2014, Vol. 36 ›› Issue (4): 274-279.

• 科技进展 • 上一篇    下一篇

30 nm染色质纤维高级结构的研究进展

董立平陈萍李国红   

  1. ①博士研究生,②副研究员,③研究员,中国科学院生物物理研究所生物大分子国家重点实验室,北京100101
  • 收稿日期:2014-06-28 出版日期:2014-08-25 发布日期:2014-08-25

New insights into the higher-order structure of 30-nm chromatin fiber

DONG Li-ping, CHEN Ping②, LI Guo-hong   

  1. ①Ph. D. Candidate, ②Associate Professor, ③Professor, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
  • Received:2014-06-28 Online:2014-08-25 Published:2014-08-25

摘要: 真核生物的遗传物质DNA以染色质形式通过逐级折叠压缩存在于细胞核中。DNA缠绕组蛋白八聚体形成核小体,相邻的核小体由连接DNA串联起来形成染色质的一级结构:核小体串珠结构(beads-on-a-string)。一级结构进一步折叠形成30 nm染色质纤维。近30多年来,30 nm染色质纤维高级结构的解析一直是困扰分子生物学家们的一大难题。研究者利用电镜和X射线晶体学等生物物理学方法对30 nm染色质纤维结构进行研究,提出30 nm结构的两大模型:螺线管(solenoid)模型和Z字结构(zig-zag)模型。笔者综述了30 nm染色质纤维结构解析方面的研究进展,并着重阐述最近利用冷冻电镜方法解析的30 nm染色质结构,即以四个核小体为结构单元的左手双螺旋结构模型,最后对30 nm染色质纤维在体内是否存在,以及它在表观遗传调控中可能发挥的重要作用等问题进行了讨论和展望。

关键词: 30 nm染色质纤维, 螺线管模型, Z字结构模型, 左手双螺旋, 冷冻电镜技术, 核小体, 组蛋白H1

Abstract: Genomic DNA in the eukaryotic cells is hierarchically folded by histones into chromatin to fit inside the nucleus. DNA wraps around the histone octamers to form nucleosomes, which are connected by linker DNA to form a “beads-on-a-string” nucleosomal array—the primary structure of chromatin. The nucleosomal array is further folded into a condensed 30-nm chromatin fiber. In past three decades, the structure of 30-nm chromatin fiber has been remained as one of the fundamental problems in molecular biology. Based on the early studies of electron microscopy, X-ray crystallography and other biophysical methods, two classic structural models have been hypothesized: the solenoid model and the zig-zag model. Here we review the recent research progresses on the structure of 30-nm chromatin fiber and focus on the recent cryo-EM study of 30-nm chromatin structure which is revealed as a left-handed double helix twisted by tetra-nucleosome units. In addition, we discuss the physiological relevance of 30-nm chromatin fiber in vivo and the perspective on its structural dynamics in epigenetic regulations.