Chromatin as dynamic 10-nm fibers.

Kazuhiro Maeshima,Ryosuke Imai,Tadasu Nozaki,Sachiko Tamura

doi:10.1007/s00412-014-0460-2

Abstract

Since Flemming described a nuclear substance in the nineteenth century and named it “chromatin,” this substance has fascinated biologists. What is the structure of chromatin? DNA is wrapped around core histones, forming a nucleosome fiber (10-nm fiber). This fiber has long been assumed to fold into a 30-nm chromatin fiber and subsequently into helically folded larger fibers or radial loops. However, several recent studies, including our cryo-EM and X-ray scattering analyses, demonstrated that chromatin is composed of irregularly folded 10-nm fibers, without 30-nm chromatin fibers, in interphase chromatin and mitotic chromosomes. This irregular folding implies a chromatin state that is physically less constrained, which could be more dynamic compared with classical regular helical folding structures. Consistent with this, recently, we uncovered by single nucleosome imaging large nucleosome fluctuations in living mammalian cells (∼50 nm/30 ms). Subsequent computational modeling suggested that nucleosome fluctuation increases chromatin accessibility, which is advantageous for many “target searching” biological processes such as transcriptional regulation. Therefore, this review provides a novel view on chromatin structure in which chromatin consists of dynamic and disordered 10-nm fibers.

Highlights

There are 60 trillion cells in the human body
The detection of periodic structures in the chromosomal region by power spectral (Fourier transform) analysis revealed a prominent peak at 11 nm, but not at 30 nm. This cryo-electron microscopy (EM) study suggested that 30-nm chromatin fibers were essentially absent from mitotic chromosomes; we proposed that 10-nm nucleosome fibers exist in a highly disordered, interdigitated state similar to a “polymer melt” (Figs. 1 and 4) (Eltsov et al 2008; Maeshima et al 2010a)
The cryo-EM, small-angle X-ray scattering (SAXS), and ultra-small-angle X-ray scattering (USAXS) data suggest that irregularly folded 10-nm nucleosome fibers form the bulk structure of human interphase chromatin and mitotic chromosomes (Nishino et al 2012; Joti et al 2012)

Summary

Introduction

There are 60 trillion cells in the human body. Each cell contains 2 m of genomic DNA in a small nucleus with an approximately 10-μm diameter (a volume of only ∼100 fL to 1 pL), and yet, it is able to search and read the information in its genomic DNA to execute diverse cellular functions. The “radial loop model” assumes that a 30-nm chromatin fiber folds into radially oriented loops to form mitotic chromosomes (Fig. 2c) (Paulson and Laemmli 1977; Laemmli et al 1978; Marsden and Laemmli 1979). This cryo-EM study suggested that 30-nm chromatin fibers were essentially absent from mitotic chromosomes; we proposed that 10-nm nucleosome fibers exist in a highly disordered, interdigitated state similar to a “polymer melt”

Results

Conclusion