Tài liệu Báo cáo khoa học: Chromatin under mechanical stress: from single 30 nm fibers to single

MINIREVIEW

Chromatin under mechanical stress: from single 30 nm

fibers to single nucleosomes

Jan Bednar1,2,3 and Stefan Dimitrov4

1 CNRS, Laboratoire de Spectrometrie Physique, St Martin d’Heres, France

2 Charles University in Prague, First Faculty of Medicine, Institute of Cellular Biology and Pathology, Prague, Czech Republic

3 Department of Cell Biology, Institute of Physiology, Academy of Science, Prague, Czech Republic

4 Institut Albert Bonniot, Grenoble, France

Introduction

Since the pioneering use of micromechanical and single

molecule manipulation approaches to probe biological

systems back in the late 1980s and 1990s (e.g. [1–5]),

their use has continuously expanded. In this review we

will focus mainly on the approaches using optical and

magnetic tweezers for studying the structure and con￾formational transitions of chromatin.

The basic repeating unit of chromatin, the nucleo￾some, represents the first level of the chromatin organi￾zation [6]. The major part of the nucleosome (termed

the chromatosome [7]) is composed of an octamer of

core histones (two each of H2A, H2B, H3 and H4), a

linker histone and 166 bp ( 56 nm) of DNA [6].

The histone octamer alone associates with 146 bp of

DNA ( 50 nm) wrapped round in 1.65 left-handed

superhelical turns (Fig. 1) to form the nucleosome core

particle (NCP), the structure of which has been solved

to 1.9 A˚ resolution by X-ray crystallography [8]. The

neighboring chromatosomes are connected by linker

DNA.

The linear array of nucleosomes folds into 30 nm

fiber, the second level of chromatin organization. The

linker histones and the core histone NH2 tails and

their post-translational modifications are essential for

both the folding process and the maintenance of the

chromatin fiber [9–11] as well as for the maintenance

Keywords

chromatin, micro-manipulation, nucleosome,

optical tweezers

Correspondence

J. Bednar, CNRS, Laboratoire de

Spectrometrie Physique, UMR 5588, BP87,

140 Av. de la Physique, 38402 St Martin

d’Heres Cedex, France

Fax: +33 476 51 45 44

Tel: +33 476 51 47 61

E-mail: [email protected]

(Received 22 November 2010, revised 7

April 2011, accepted 28 April 2011)

doi:10.1111/j.1742-4658.2011.08153.x

About a decade ago, the elastic properties of a single chromatin fiber and,

subsequently, those of a single nucleosome started to be explored using

optical and magnetic tweezers. These techniques have allowed direct mea￾surements of several essential physical parameters of individual nucleo￾somes and nucleosomal arrays, including the forces responsible for the

maintenance of the structure of both the chromatin fiber and the individual

nucleosomes, as well as the mechanism of their unwinding under mechani￾cal stress. Experiments on the assembly of individual chromatin fibers have

illustrated the complexity of the process and the key role of certain specific

components. Nevertheless a substantial disparity exists in the data reported

from various experiments. Chromatin, unlike naked DNA, is a system

which is extremely sensitive to environmental conditions, and studies car￾ried out under even slightly different conditions are difficult to compare

directly. In this review we summarize the available data and their impact

on our knowledge of both nucleosomal structure and the dynamics of

nucleosome and chromatin fiber assembly and organization.

Abbreviations

ACF, ATP-dependent chromatin assembly and remodeling factor; HMG, high-mobility group; NAP-1, nucleosome assembly protein 1;

NCP, nucleosome core particle.

FEBS Journal 278 (2011) 2231–2243 Journal compilation ª 2011 FEBS. No claim to original French government works 2231