Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Discovery reveals chromosomes organize into 'yarns'

12.04.2012
Chromosomes, the molecular basis of genetic heredity, remain enigmatic 130 years after their discovery in 1882 by Walther Flemming.

New research published online in Nature by the team of Edith Heard, PhD, from the Curie Institute and Job Dekker, PhD, from the University of Massachusetts Medical School (UMMS), reveals a new layer in the complex organization of chromosomes. The scientists have shown that chromosomes fold in a series of contiguous "yarns" that harbor groups of genes and regulatory elements, bringing them in contact with each other and allowing them to work in a coordinated manner during development.

Chromosomes are relatively large molecules that, when spread out, can measure up to the length of an entire human arm. Despite their size, however, they are actually confined within the small space of the cell nucleus which is just a few micrometers in size. Furthermore, within each cell nucleus are multiple chromosomes. In humans, for example, there are 23 pairs of chromosomes. In order to fit all this material into this small area, chromosomes are folded, compacted and mingled in the three-dimensional space of the nucleus.

So do chromosomes fill the nucleus just like spaghetti fills a plate? "Not quite," said Elphege Nora, PhD, a post-doctoral fellow on the team of Dr. Heard, head of the Genetics and Developmental Biology Lab at the Curie Institute. "Chromosome folding follows a pattern, and this actually turns out to be important for ensuring their proper function."

A chromosome looks like a series of tiny yarns

"We have known for decades that the DNA of individual genes is wrapped around nucleosomes to form the classical 'beads-on-a-string' structure," said Dekker, co-director of the Program in Systems Biology at UMMS. "Our new study now shows that these beads-on-a-string subsequently fold up to form 'yarns-on-a-string,' where each yarn is a group of genes. This domainal organization of chromosomes represents a previously unknown higher order level of folding that we believe is a fundamental organizing principle of genomes."

These globule-like yarns span anything from a few hundred thousand to a million base pairs, explained Heard. Base pairs (abbreviated as A, C, G and Ts) are the genome's unit of measurement, and a person's DNA consists of over 3 billion pairs. "The real surprise, however, lies in how this spatial folding of chromosomes links up to their functional organization," said Heard. "This chromosome folding pattern brings together, into the same 'yarn,' several genes, up to 10 of them, or even more."

However, there are not just genes in these yarns. So called "regulatory genomic elements," that can control the activity of neighboring genes like switches are also found clustered together with the genes in these chromosomal yarns. A group of genes belonging to the same yarn will therefore be likely to contact a similar set of regulatory elements, and this can result in the coordinated activity of these genes during development.

These new observations shed some light on several long-standing mysteries of genetics, such as the reason why some DNA mutations can end up affecting genes that are located thousands or even a million base pairs away.

"The cell nucleus is packed with genes, and the cell is faced with the challenge to turn on or off each one of them correctly," said Dekker. "By organizing groups of genes in isolated domains, or yarns that do not mingle or mix with other genes, the cell has solved the problem of how to regulate groups of genes coordinately and without interference from other genes."

However, damaging one of these "chromosome yarns" can lead to the misbehavior of all the genes it contains. "The three-dimensional organization of chromosomes allows distal genomic elements to be brought together and to functionally interact with each other. At certain points during development it is thus possible to precisely orchestrate the activity of genes that are far away from each other on the linear chromosome thread, but that are actually in contact physically, within a chromosome yarn," said Nora. "The down side of this type of organization is that a single mutation altering the organization of such a 'chromosome yarn' can affect a whole group of genes."

Three-dimensional folding provides shortcuts through the chromosome

"Together with Job Dekker, who has pioneered chromosome conformation capture technologies, we have discovered these principles by studying a critical region of the X chromosome, the X-inactivation center," said Heard. "Thanks to a parallel study conducted by the team of Bing Ren, PhD, at the University of San Diego (and published in Nature alongside the Heard and Dekker study), we now know that the principles of chromosome folding we have seen on the X chromosome actually apply to the whole mouse and human genomes."

Beyond advancing our fundamental understanding of chromosome biology, these studies also open up new avenues for studying certain diseases, such as genetic disorders that are due to mutations in the DNA sequence which disrupt the proper activity of certain genes. Sometimes the mutation causing these defects is not directly in the gene, but affects one of its regulatory elements somewhere in its extended chromosomal neighborhood. Finding such mutations along the chromosome has been a bit like looking for a needle in a haystack because scientists did not know which genes were partnered with which regulatory elements. The hunt for such mutations can now be directed first to the chromosomal region most likely to harbor the regulatory elements of the misbehaving gene – inside the chromosome "yarn" to which that gene belongs.

About the University of Massachusetts Medical School

The University of Massachusetts Medical School, one of the fastest growing academic health centers in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $277 million in research funding annually, 80 percent of which comes from federal funding sources. The mission of the Medical School is to advance the health and well-being of the people of the commonwealth and the world through pioneering education, research, public service and health care delivery with its clinical partner, UMass Memorial Health Care. For more information, visit www.umassmed.edu

Jim Fessenden | EurekAlert!
Further information:
http://www.umassmed.edu

More articles from Life Sciences:

nachricht A Varied Menu
25.03.2019 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht Key evidence associating hydrophobicity with effective acid catalysis
25.03.2019 | Tokyo Metropolitan University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The taming of the light screw

DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.

The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...

Im Focus: Magnetic micro-boats

Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.

The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Laser processing is a matter for the head – LZH at the Hannover Messe 2019

25.03.2019 | Trade Fair News

A Varied Menu

25.03.2019 | Life Sciences

‘Time Machine’ heralds new era

25.03.2019 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>