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posted by Fnord666 on Wednesday August 02 2017, @01:17AM   Printer-friendly
from the ...know-when-to-fold-'em dept.

Salk scientists solve longstanding biological mystery of DNA organization — Researchers image 3D genome in nucleus of living human cell for the first time.

Stretched out, the DNA from all the cells in our body would reach Pluto. So how does each tiny cell pack a two-meter length of DNA into its nucleus, which is just one-thousandth of a millimeter across?

[...] In the tour de force study, described in Science on July 27, 2017, the Salk researchers identified a novel DNA dye that, when paired with advanced microscopy in a combined technology called ChromEMT, allows highly detailed visualization of chromatin structure in cells in the resting and mitotic (dividing) stages. By revealing nuclear chromatin structure in living cells, the work may help rewrite the textbook model of DNA organization and even change how we approach treatments for disease.

"One of the most intractable challenges in biology is to discover the higher-order structure of DNA in the nucleus and how is this linked to its functions in the genome," says Salk Associate Professor Clodagh O'Shea, a Howard Hughes Medical Institute Faculty Scholar and senior author of the paper. "It is of eminent importance, for this is the biologically relevant structure of DNA that determines both gene function and activity."

[...] With their 3D microscopy reconstructions, the team was able to move through a 250 nm x 1000 nm x 1000 nm volume of chromatin's twists and turns, and envision how a large molecule like RNA polymerase, which transcribes (copies) DNA, might be directed by chromatin's variable packing density, like a video game aircraft flying through a series of canyons, to a particular spot in the genome. Besides potentially upending the textbook model of DNA organization, the team's results suggest that controlling access to chromatin could be a useful approach to preventing, diagnosing and treating diseases such as cancer.

"We show that chromatin does not need to form discrete higher-order structures to fit in the nucleus," adds O'Shea. "It's the packing density that could change and limit the accessibility of chromatin, providing a local and global structural basis through which different combinations of DNA sequences, nucleosome variations and modifications could be integrated in the nucleus to exquisitely fine-tune the functional activity and accessibility of our genomes."

I'm by no means a geneticist. Nearly anyone can take a length of rope and coil it into a compact shape. Doing it in such a way that it can be readily uncoiled is quite another thing. So how does DNA get 'coiled up' without getting tied full of knots? Folding and unfolding, then, are critical and it seems that these researchers have made some key discoveries into this.

[Aside: For those who may not be aware, SoylentNews has an official Folding@Home team. Out of nearly a quarter-million teams, I'm please to report that we have broken into the ranks of the top 300 teams in the world! At the time of this writing, the official Folding@Home site reports we are ranked 287 of 226863. More information at the Folding@home main site. We are team number 230319. Come join the team as we help in the fight against Huntington's, Parkinson's, and many other diseases. --martyb]


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  • (Score: 2) by requerdanos on Wednesday August 02 2017, @11:52AM (2 children)

    by requerdanos (5997) Subscriber Badge on Wednesday August 02 2017, @11:52AM (#547898) Journal

    Stretched out, the DNA from all the cells in our body would reach Pluto.

    Wow, that's amazingly... vague.

    How far is that? Space.Com [space.com] tells us that...

    The planets in the solar system travel in elliptical orbits rather than perfect circles, and so the distances between them are constantly changing. At its most distant, when the two bodies are on the opposite sides of the sun from one another, Pluto lies 4.67 billion miles (7.5 billion kilometers) from Earth. At their closest, the two are only 2.66 billion miles (4.28 billion km) apart.

    And even that "Somewhere between 4.2 billion and 7.5 billion km" measurement is idealized. What if you're standing on a part of Earth that's not facing towards Pluto, and your DNA has to wrap around, first? That's extra uncertainty right there.

    Even "Linear Libraries of Congress" would be a better measure than this.

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  • (Score: 1, Insightful) by Anonymous Coward on Wednesday August 02 2017, @12:29PM (1 child)

    by Anonymous Coward on Wednesday August 02 2017, @12:29PM (#547905)

    I'm surprised you didn't notice that the next sentence says that the DNA for a given cell would only stretch out to be 2 meters long, a far less crazy number.

    Let's check it. I'd estimate 1 nucleotide is ~0.34e-9 m (at first I was thinking ~1e-9 nm like amino acids but then actually looked it up[1]) and the human genome has ~3.25e9 pairs of these. So ~2.21 meters worth per cell. Then there are ~3e13 cells in the adult body[2] giving 6e13 meters worth of dna. That is 66300 billion meters or 66.3 billion km.

    The reference regarding the average number of human cells calls their estimate a "starting point" though, they say most estimates are found in textbooks and are do not explain where the numbers came from (this was published in 2013, wtf have biologists been doing for decades that we don't know basic parameters like this?). Anyway, the estimates range from 1e-12 to 1-16 cells per body (on average), so the distance could range from 2e12 to 2e16 meters (2-20,000 billion km)

    I'd say number of human cells is the biggest source of uncertainty here.

    [1] http://faculty.washington.edu/trawets/vc/theory/dna/ [washington.edu]
    [2] https://www.ncbi.nlm.nih.gov/pubmed/23829164 [nih.gov]

    • (Score: 0) by Anonymous Coward on Wednesday August 02 2017, @12:32PM

      by Anonymous Coward on Wednesday August 02 2017, @12:32PM (#547908)

      That should say "~1 nm like amino acids".