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 Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University

nachricht How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>