Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists decipher the 3-D structure of the human genome

09.10.2009
Fractal globule architecture packs two meters of DNA into each human cell, avoids knots

Scientists have deciphered the three-dimensional structure of the human genome, paving the way for new insights into genomic function and expanding our understanding of how cellular DNA folds at scales that dwarf the double helix.

In a paper featured this week on the cover of the journal Science, they describe a new technology called Hi-C and apply it to answer the thorny question of how each of our cells stows some three billion base pairs of DNA while maintaining access to functionally crucial segments. The paper comes from a team led by scientists at Harvard University, the Broad Institute of Harvard and MIT, University of Massachusetts Medical School, and the Massachusetts Institute of Technology.

"We've long known that on a small scale, DNA is a double helix," says co-first author Erez Lieberman-Aiden, a graduate student in the Harvard-MIT Division of Health Science and Technology and a researcher at Harvard's School of Engineering and Applied Sciences and in the laboratory of Eric Lander at the Broad Institute. "But if the double helix didn't fold further, the genome in each cell would be two meters long. Scientists have not really understood how the double helix folds to fit into the nucleus of a human cell, which is only about a hundredth of a millimeter in diameter. This new approach enabled us to probe exactly that question."

The researchers report two striking findings. First, the human genome is organized into two separate compartments, keeping active genes separate and accessible while sequestering unused DNA in a denser storage compartment. Chromosomes snake in and out of the two compartments repeatedly as their DNA alternates between active, gene-rich and inactive, gene-poor stretches.

"Cells cleverly separate the most active genes into their own special neighborhood, to make it easier for proteins and other regulators to reach them," says Job Dekker, associate professor of biochemistry and molecular pharmacology at UMass Medical School and a senior author of the Science paper.

Second, at a finer scale, the genome adopts an unusual organization known in mathematics as a "fractal." The specific architecture the scientists found, called a "fractal globule," enables the cell to pack DNA incredibly tightly -- the information density in the nucleus is trillions of times higher than on a computer chip -- while avoiding the knots and tangles that might interfere with the cell's ability to read its own genome. Moreover, the DNA can easily unfold and refold during gene activation, gene repression, and cell replication.

"Nature's devised a stunningly elegant solution to storing information -- a super-dense, knot-free structure," says senior author Eric Lander, director of the Broad Institute, who is also professor of biology at MIT, and professor of systems biology at Harvard Medical School.

In the past, many scientists had thought that DNA was compressed into a different architecture called an "equilibrium globule," a configuration that is problematic because it can become densely knotted. The fractal globule architecture, while proposed as a theoretical possibility more than 20 years ago, has never previously been observed.

Key to the current work was the development of the new Hi-C technique, which permits genome-wide analysis of the proximity of individual genes. The scientists first used formaldehyde to link together DNA strands that are nearby in the cell's nucleus. They then determined the identity of the neighboring segments by shredding the DNA into many tiny pieces, attaching the linked DNA into small loops, and performing massively parallel DNA sequencing.

"By breaking the genome into millions of pieces, we created a spatial map showing how close different parts are to one another," says co-first author Nynke van Berkum, a postdoctoral researcher at UMass Medical School in Dekker's laboratory. "We made a fantastic three-dimensional jigsaw puzzle and then, with a computer, solved the puzzle."

Lieberman-Aiden, van Berkum, Lander, and Dekker's co-authors are Bryan R. Lajoie of UMMS; Louise Williams, Ido Amit, and Andreas Gnirke of the Broad Institute; Maxim Imakaev and Leonid A. Mirny of MIT; Tobias Ragoczy, Agnes Telling, and Mark Groudine of the Fred Hutchison Cancer Research Center and the University of Washington; Peter J. Sabo, Michael O. Dorschner, Richard Sandstrom, M.A. Bender, and John Stamatoyannopoulos of the University of Washington; and Bradley Bernstein of the Broad Institute and Harvard Medical School.

This work was supported by the Fannie and John Hertz Foundation, the U.S. Department of Defense, the National Science Foundation, the National Space Biomedical Research Institute, the National Human Genome Research Institute, the American Society of Hematology, the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Keck Foundation, and the National Institutes of Health.

Steve Bradt | EurekAlert!
Further information:
http://www.harvard.edu

More articles from Life Sciences:

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
21.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
21.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>