Findings from quantitative analysis of chromatin structure challenge classical model of static regularity

Jul 20, 2012
Figure 1: Chromosomes (left) consist of tightly compacted and irregularly folded nucleosome fibers. Credit: Reproduced from Ref. 1 © 2012 Yoshinori Nishino et al., RIKEN SPring-8 Center

The DNA in the human genome is organized into irregularly folded fibers during cell division, according to a recent study by a team of researchers led by Kazuhiro Maeshima of the RIKEN SPring-8 Center and RIKEN Advanced Science Institute in Japan. 

is wrapped around proteins called histones to form nucleosome , which are tightly compressed into the chromosomes by large protein complexes called condensins (Fig. 1). Many previous studies suggest that nucleosomes are organized into regular fiber structures that are 30 nanometers in diameter, which led to the classical model of overall chromosome structure. However, other studies suggest that these regular fiber structures exist only in specialized cell types.

To resolve these conflicting results, Maeshima and his colleagues investigated chromosome structure in mitotic, or dividing, HeLa cells using three different techniques: cryo-electron microscopy, which allows for observation of frozen, hydrated biological structures at high resolution without producing the artifacts seen in conventional EM; small-angle x-ray scattering (SAXS), which detects repeating structures in solutions of biological samples; and ultra-small x-ray scattering (USAXS), a newly developed type of SAXS that can resolve repeating structures across larger dimensions.

All three techniques produced consistent results. The researchers detected repeating structures at approximately every 11 nanometers, but not at longer distances, suggesting that chromatin is organized like beads on a string with an irregular folding pattern. The USAXS method further revealed that the chromosomes have a fractal nature: the same organization repeats itself at different scales, and that is the structures arrange into a rod shape.

Maeshima and colleagues propose two possible explanations for the rod-shaped and large-scale organization of the chromosome. One is that the condensins bind to specific sites in the DNA, causing it to form self-assembling loops that interact with each other and produce repeating structures along the axis of the chromosome. Alternatively, the formation of regularly repeating looped structures alone might be sufficient to generate the observed rod shape because of repulsive forces between adjacent loops.

The researchers predict that irregular folding would make chromosomes more flexible: this type of organization has fewer physical constraints than a regular structure. They also suggest that irregular folding is common to in interphase, or non-dividing cells, as it makes DNA more accessible to the molecular machinery for RNA transcription and DNA replication. 

“We focused on chromosomes in dividing cells,” says Maeshima, “but we assume that a similar irregular folding also exists in interphase cells, and are now assessing that assumption.”

Explore further: Mycologist promotes agarikon as a possibility to counter growing antibiotic resistance

More information: Nishino, Y., et al. Human mitotic chromosomes consist predominantly of irregularly folded nucleosome fibres without a 30-nm chromatin structure. The EMBO Journal 31, 1644–1653 (2012)

add to favorites email to friend print save as pdf

Related Stories

Shaping up for cell division

Nov 04, 2011

The shape of chromosomes is determined by the relative levels of key protein complexes, research conducted by Keishi Shintomi and Tatsuya Hirano of the RIKEN Advanced Science Institute has shown.

Elusive Z- DNA found on nucleosomes

Jan 20, 2012

New research published in BioMed Central's open access journal Cell & Bioscience is the first to show that left-handed Z-DNA, normally only found at sites where DNA is being copied, can also form on nucleosomes.

Study Confirms DNA Repair Model After 26 Years

Apr 14, 2010

(PhysOrg.com) -- UC Davis researchers have confirmed a central idea about chromosome repair, more than a quarter century after it was first proposed. The finding is important to scientists who seek to understand DNA repair, ...

DNA constraints control structure of attached macromolecules

Jun 28, 2005

A new method for manipulating macromolecules has been developed by researchers at the University of Illinois at Urbana-Champaign. The technique uses double-stranded DNA to direct the behavior of other molecules. In previous ...

Recommended for you

YEATS protein potential therapeutic target for cancer

Oct 23, 2014

Federal Express and UPS are no match for the human body when it comes to distribution. There exists in cancer biology an impressive packaging and delivery system that influences whether your body will develop cancer or not.

Precise and programmable biological circuits

Oct 23, 2014

A team led by ETH professor Yaakov Benenson has developed several new components for biological circuits. These components are key building blocks for constructing precisely functioning and programmable bio-computers.

User comments : 0