Nucleosome structure and dynamics are coming of age

Abstract

Since the first high-resolution structure of the nucleosome was reported in 1997, the available information on chromatin structure has increased very rapidly. Here, we review insights derived from cutting-edge biophysical and structural approaches applied to the study of nucleosome dynamics and nucleosome-binding factors, with a focus on the experimental advances driving the research. In addition, we highlight emerging challenges in nucleosome structural biology.

Figure 1:. Nucleosome structure

A: Nucleosome disc view, model derived from PDB entries 1KX5 and 1ZBB (DNA from 1ZBB, histone octamer core from 1KX5). B: Electrostatic potential of the nucleosome surface (electrostatic potential calculated from PDB 1KX5, using APBS within PyMOL version 2.2.0). C: Nucleosomal DNA and linker DNA (from PDB entry 1ZBB). Along the 2-fold axis, nucleosomal DNA (145-147 bp) can be divided into two “gyres” (about 72 bp each). The super-helical location (SHL) designation represents the position of each major groove facing inward. The dyad (center of the nucleosomal DNA) is defined as position 0. The numbers “1-7” highlight the SHL on DNA. Linker DNA is the extra-nucleosomal DNA which locates next to the entry/exit site of nucleosomal DNA.

Figure 2:. Dynamics of nucleosome unwrapping

A: CryoEM structures of a canonical nucleosome (PDB entry 6ESF) and a partially unwrapped nucleosome (PDB entry 6ESH). Rate constants of spontaneous unwrapping and rewrapping, determined by stopped-flow spectroscopy, are indicated. B: Location of post-translational modifications that have been studied for their effect on nucleosome unwrapping: at the DNA entry/exit site, at SHL +/−3 (about 35 bp into the nucleosome) and at the dyad. The effects of these post-translational modifications on nucleosome dynamics are indicated. From PDB entry 1KX5.

Figure 3:. Structures of chromatin-binding factor complexes

PDB entries of the structures shown in the figure. “1” indicates structures obtained by crystallography. “2” indicates structural models built from single-particle cryoEM maps. “2*” represents docking models generated to interpret cryoEM maps. A: Proteins targeting the surface of nucleosome: a1, small protein fragments or polypeptides recognizing the acidic patch on the nucleosome surface; a2, proteins recognizing both the acidic patch and epigenetic marks on the nucleosome surface; a3, proteins binding to both histones and nucleosomal DNA on the nucleosome surface (the acidic patch also plays an important role in complex a3.1 but not in a3.2). B: Proteins invading nucleosomal DNA gyres. C: Proteins interacting with linker DNA.