Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

28.07.2017

Structure determines function. Revealing the dynamic and structural interactions of DNA in the nucleus has been a critical missing link in genotype to phenotype

Sixty-four years ago, James Watson and Francis Crick described the now-iconic double helix structure of DNA. In a new paper, published in the July 28, online issue of Science, a team of researchers at the University of California San Diego School of Medicine and the Salk Institute for Biological Studies describe development and application of new electron microscopic imaging tools and a selective stain for DNA to visualize the three-dimensional structure of chromatin -- a complex of molecules that helps pack six feet of DNA into each cell nucleus, construct chromosomes and control gene expression and DNA replication.


Chromatin structure determines the function of the human genome. To visualize chromatin of intact cells, a method called ChromEMT labels DNA and paints a metal dust over chromatin. In the composite image above, a black-and-white electron micrograph of a cell nucleus is half stained by ChromEMT. The stained nucleus is then imaged by electron microscopy to generate a 3D volume that reveals chromatin structure and organization. The circular magnified image shows ChromEMT stained chromatin (dark structures) overlapping with a contour map of chromatin density (blue-low, green-medium, red-high density). Analysis reveals that chromatin is organized as 5 to 24 nm diameter polymer chains that pack in wide distribution of density in interphase resting cells, but uniform density in mitotic cells. Two models of nucleosome orientations in the chromatin chain are shown at bottom right.

Credit: Horng D. Ou, Salk Institute.

"The primary functions of chromatin are fundamental," said study co-lead Mark Ellisman, PhD, Distinguished Professor of Neurosciences and Bioengineering and director of the National Center for Microscopy and Imaging Research (NCMIR) at UC San Diego. "It efficiently packages DNA to fit inside the cell nucleus, making it possible for chromosomes and cells to divide and replicate safely and correctly. It's a basic, working element of life."

The new findings and the methods developed allow them help resolve an on-going, persistent debate about the actual structure of chromatin, long poorly understood. DNA wraps around complex structures called nucleosomes. This chain of disks was thought to organize into increasingly thicker fibers that progressively form what are seen as condensed chromosomes in dividing cells.

... more about:
»3D »DNA »Microscopy »cell nucleus »chromosomes »fibers »human cell

Ellisman, with co-senior author Clodagh O'Shea, PhD, an associate professor at Salk and Howard Hughes Medical Institute Faculty Scholar, and colleagues demonstrate that this model of hierarchical packing into thicker and thicker cables is not correct. They developed a new imaging approach called ChromEMT, which combines an advanced form of electron microscopy tomography, developed at NCMIR, with a new labeling method to selectively enhance electron scattering and thus the specific contrast associated with DNA to directly image within cells the threads of this important core element of the genome.

Ellisman said that it is now clear that the biological functions and activity of our genomes in the nucleus are not determined by linear DNA sequence information alone. Instead, it is the local nucleosome structure combined with its global 3D organization in the nucleus that determines gene expression and cell fate. ChromEMT enables DNA and chromatin to be visualized across this critical set of biological and structural scales in single cells for the first time.

O'Shea said the findings reveal that nucleus DNA assembles five to 24-nanometer-diameter chromatin chains in a diversity of 3D conformations and motifs. "In contrast to ordered and rigid fibers, chromatin is a flexible chain that can collapse and pack together into 3D domains that have a wide range of different concentration densities," she said. "This provides exciting new insights into how different gene sequences, interactions and epigenetic modifications can be integrated at the level of chromatin structure to regulate gene expression and inherited and maintained through cell division."

O'Shea and Ellisman are co-principal investigators in a project funded by the 4D Nucleome Consortium to better understand how DNA is arranged within a cell nucleus in three dimensions plus time; and how these changes in DNA organization affect human health and disease. Their goal is to use ChromEMT to "crack the cell nucleus" and decipher how a cell's nucleus or control center oversees cell growth, metabolism and reproduction. They are now developing additional labels that can be combined with ChromEMT to visualize the structural basis of gene silencing and how viral and cancer proteins remodel DNA to drive pathological replication.

###

Co-authors of this study include: Horng D. Ou, Salk Institute; Sebastien Phan, Thomas J. Deerinck and Andrea Thor, UC San Diego.

About NCMIR

The National Center for Microscopy and Imaging Research, based at UC San Diego, is a world-leading center whose mission is to develop technologies to bridge understanding of biological systems between the gross anatomical and molecular scales and to make these technologies broadly available to biomedical researchers. NCMIR provides expertise, infrastructure, technological development and an environment in which new information about the 3D ultrastructure of tissues, cells and macromolecular complexes may be accurately and easily obtained and analyzed. It is supported by the National Institute of General Medical Sciences, part of the National Institutes of Health.

Media Contact

Scott LaFee
slafee@ucsd.edu
858-249-0456

 @UCSanDiego

http://www.ucsd.edu 

Scott LaFee | EurekAlert!

Further reports about: 3D DNA Microscopy cell nucleus chromosomes fibers human cell

More articles from Health and Medicine:

nachricht Purdue cancer identity technology makes it easier to find a tumor's 'address'
16.11.2018 | Purdue University

nachricht Microgel powder fights infection and helps wounds heal
14.11.2018 | Michigan Technological University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

Purdue cancer identity technology makes it easier to find a tumor's 'address'

16.11.2018 | Health and Medicine

Good preparation is half the digestion

16.11.2018 | Life Sciences

Microscope measures muscle weakness

16.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>