Only Half of Chromosome is DNA, New Study Reveals

DNA makes up only half of the material inside chromosomes, according to a new study published in the journal Molecular Cell. Up to 47% of their structure is a mysterious sheath that surrounds the genetic material.

Booth et al. develop a microscopy method called 3D-CLEM. Using this approach, they find that a large portion of mitotic chromosomes is not composed of chromatin, challenging classical perceptions of chromosomes. Image credit: Booth et al, doi: 10.1016/j.molcel.2016.10.009.

Since their first discovery in 1882, mitotic chromosomes have been a subject of intense study.

Remarkably, despite the significant developments of light and electron microscopy over the intervening years, the detailed organization of chromosomes has remained a mystery.

A research team headed by University of Edinburgh scientists developed a precise microscopy method that allows them to study the structure of chromosomes in detail.

The method, called 3D-CLEM, combines light and scanning electron microscopy with computational modeling software to produce high-resolution 3D images of chromosomes.

“3D-CLEM has allowed us to determine the length, width, surface area, volume, and DNA packing density of all normal human chromosomes and to determine the DNA content of a small synthetic artificial chromosome,” the authors explained.

“The imaging technique we have developed to study chromosomes is truly groundbreaking,” added study co-lead author Dr. Daniel Booth, of the University of Edinburgh’s School of Biological Sciences.

“Defining the structure of all 46 human chromosomes for the first time has forced us to reconsider the idea that they are composed almost exclusively of chromatin, an assumption that has gone largely unchallenged for almost 100 years.”

Top: a mitotic RPE (retinal pigment epithelium) cell. Bottom: images show the full chromosome complement (i) and segmented chromosomes (ii); arrows point to examples of individual chromosomes shown in the zoom panels; these include examples of metacentric (cyan) and submetacentric (red, orange) chromosomes. Scale bar – 10 ?m. Image credit: Booth et al, doi: 10.1016/j.molcel.2016.10.009.

Analysis of the images reveals that material containing DNA and supporting proteins — known as chromatin — accounts for between 53 and 70% of the total contents of chromosomes.

The remaining 30 to 47% is composed of the chromosome periphery.

While the precise function of this sheath is unknown, Dr. Booth and co-authors suggest it may keep chromosomes isolated from one another during the key process of cell division.

“This so-called chromosome periphery could help to prevent errors from occurring when cells divide — a hallmark of some forms of cancer and diseases associated with birth defects,” they said.

“We now have to re-think how chromosomes are built and how they segregate when cells divide, since the genetic material is covered by this thick layer of other material,” added study co-lead author Prof. Bill Earnshaw, also from the University of Edinburgh’s School of Biological Sciences.

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Daniel G. Booth et al. 2016. 3D-CLEM Reveals that a Major Portion of Mitotic Chromosomes is Not Chromatin. Molecular Cell 64 (4): 790-802; doi: 10.1016/j.molcel.2016.10.009