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 Oestrogen regulates pathological changes of bones via bone lining cells
28.07.2017 | Veterinärmedizinische Universität Wien

nachricht Programming cells with computer-like logic
27.07.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Abrupt motion sharpens x-ray pulses

Spectrally narrow x-ray pulses may be “sharpened” by purely mechanical means. This sounds surprisingly, but a team of theoretical and experimental physicists developed and realized such a method. It is based on fast motions, precisely synchronized with the pulses, of a target interacting with the x-ray light. Thereby, photons are redistributed within the x-ray pulse to the desired spectral region.

A team of theoretical physicists from the MPI for Nuclear Physics (MPIK) in Heidelberg has developed a novel method to intensify the spectrally broad x-ray...

Im Focus: Physicists Design Ultrafocused Pulses

Physicists working with researcher Oriol Romero-Isart devised a new simple scheme to theoretically generate arbitrarily short and focused electromagnetic fields. This new tool could be used for precise sensing and in microscopy.

Microwaves, heat radiation, light and X-radiation are examples for electromagnetic waves. Many applications require to focus the electromagnetic fields to...

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

 
Latest News

New 3-D imaging reveals how human cell nucleus organizes DNA and chromatin of its genome

28.07.2017 | Health and Medicine

Heavy metals in water meet their match

28.07.2017 | Power and Electrical Engineering

Oestrogen regulates pathological changes of bones via bone lining cells

28.07.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>