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| Roger Bagula... |
 Posted: Sat Oct 10, 2009 2:53 pm |
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http://www.sciencedaily.com/releases/2009/10/091008142957.htm
3-D Structure Of Human Genome: Fractal Globule Architecture Packs Two
Meters Of DNA Into Each Cell
ScienceDaily (Oct. 8, 2009) — 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.
Journal reference:
1. Lieberman-Aiden et al. Comprehensive mapping of long-range
interactions reveals folding principles of the human genome. Science,
2009; DOI: 10.1126/science.1181369 |
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| Roger Bagula... |
| Posted: Sat Oct 10, 2009 3:18 pm |
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Access : Cells go fractal : Nature News
http://www.nature.com/news/2009/090904/full/news.2009.880.html
Published online 4 September 2009 | Nature | doi:10.1038/news.2009.880
News
Cells go fractal
Mathematical patterns rule the behaviour of molecules in the nucleus.
Claire Ainsworth
The maths behind the rugged beauty of a coastline may help to keep
cell biology
in order, say researchers in Germany. Fractals — rough shapes that
look the same
at all scales — could explain how the cell's nucleus holds molecules
that manage
our DNA in the right location. |
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