Chromatin fiber structural motifs as regulatory hubs of genome function?

Manuela Moraru,Thomas Schalch

doi:10.1042/ebc20180065

Abstract

Nucleosomes cover eukaryotic genomes like beads on a string and play a central role in regulating genome function. Isolated strings of nucleosomes have the potential to compact and form higher order chromatin structures, such as the well-characterized 30-nm fiber. However, despite tremendous advances in observing chromatin fibers in situ it has not been possible to confirm that regularly ordered fibers represent a prevalent structural level in the folding of chromosomes. Instead, it appears that folding at a larger scale than the nucleosome involves a variety of random structures with fractal characteristics. Nevertheless, recent progress provides evidence for the existence of structural motifs in chromatin fibers, potentially localized to strategic sites in the genome. Here we review the current understanding of chromatin fiber folding and the emerging roles that oligonucleosomal motifs play in the regulation of genome function.

Highlights

The physical form of eukaryotic genomes is a complex of DNA, RNA, and proteins referred to as ‘chromatin’
Oligonucleosomes serve as preferred substrates for chromatin-associated complexes
We propose that defined oligonucleosomal structures play an important role in chromatin biology

Summary

Introduction

The physical form of eukaryotic genomes is a complex of DNA, RNA, and proteins referred to as ‘chromatin’. Significant progress has been made on the question of chromatin fiber structure in vitro by cross-linking approaches [25,26,27] and by X-ray and cryo-EM structures with sufficient resolution to resolve the linker DNA [27,28,29,30] (Figure 2) Both biochemistry and high-resolution structures support a two-start model for compact chromatin fibers with regularly spaced nucleosomes. Chromosome conformation capture experiments with nucleosomal resolution (Micro-C) have recently been developed to study chromatin fiber structure in vivo [81,82] These experiments do not show evidence for long-range order in the chromatin fiber, but are consistent with tri- and tetranucleosomal units as chromatin fiber folding motifs. One documented example of a complex associated with longer chromatin fragments is the DNA methyltrasferase DNMT3B, whose chromatin binding increases with higher levels of H1 and with longer, more compact chromatin fiber substrates in vitro and in cells [99]

Conclusions

Summary