Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists discover key patterns in the packaging of genes

15.07.2008
An effort to detect patterns of chemical changes in histones and their impact on gene expression

Although every cell of our bodies contains the same genetic instructions, specific genes typically act only in specific cells at particular times. Other genes are "silenced" in a variety of ways. One mode of gene silencing depends upon the way DNA, the genetic material, is packed in the nucleus of cells.

When packed very tightly around complexes of proteins called histones, the DNA double helix is rendered physically inaccessible to molecules that mediate gene expression. Now, a research team that includes Michael Q. Zhang, Ph.D., a professor at Cold Spring Harbor Laboratory (CSHL), has published a comprehensive analysis of modification patterns in histones.

Using a new technology called ChIP-Seq, the team identified 39 histone modifications, including a "core set" of 17 modifications that tended to occur together and were associated with genes observed to be active.

... more about:
»Cell »DNA »Histone »Zhang »activity

Modification Patterns With Different "Personalities"

Scientists have long known that chemical changes at particular locations in histone complexes influence how tightly the DNA is wrapped around the histones. "But it is important to know whether particular modifications occur together in characteristic patterns, or if these patterns can predict gene activities," Dr. Zhang explained.

At the heart of the team's efforts to determine this, Keji Zhao, Ph.D., of the National Heart, Blood, and Lung Institute of the National Institutes of Health, and his colleagues developed a method to map modifications in human white blood cells known as CD4+ T cells. First they used an enzyme to cut the DNA into short segments, which remained attached to histone "spools." For each of 39 distinct histone modifications, the scientists used an antibody to extract matching histone-DNA combinations. Finally, they used the ChIP-Seq DNA-sequencing technology to determine which parts of the genome were bound to each type of modified histone.

The team's most recent research, published in the July 2008 issue of Nature Genetics, maps the DNA locations that bind to histones containing molecular configurations called acetyl groups at 18 different positions in the "tails" of the histone proteins. The scientists combined this information with earlier maps for 19 different changes called methylation modifications, and for replacement of one of the histone proteins with a well-known variant.

The various modifications showed distinctive "personalities," each preferentially associating with particular regulatory regions of genes.

Looking for Patterns

Mapping many modifications enabled the researchers to explore whether different types tend to appear together in the same type of DNA regulatory regions. They found that some recurring combinations did occur frequently at "promoter" and "enhancer" regions in DNA, which are known to increase the activity of nearby genes. In particular, the team identified one combination of 17 modifications that was present in more than a quarter of the more than 12,000 promoter regions they examined.

On average, the genes corresponding to this "backbone" set were expressed more actively. That is to say, they were activated, setting the cellular machinery in motion to produce specific proteins, the workhorses of most life processes.

The rich relationships detected by the researchers among the various histone modifications suggests that specific combinations might carry specific meanings. Previous researchers have proposed a "histone code" hypothesis, which posits that a particular combination of modifications may be recognized by a particular protein module. Some scientists believe such histone code may determine the activity of a given gene.

But, cautions Dr. Zhang, while there are patterns, like the backbone, that are highly correlated, "none of them has exact predictive value." He maintains "there must be something else" that also affects gene activity.

Since genes with higher or lower expression levels may have the same patterns of modification, and not all active genes share a common pattern, the reality is likely more complex than a universal histone code that predicts exact gene expression level. Nonetheless, the new research provides a rich data source for understanding how specific combinations of histone modifications modulate the effects of many genes, in turn helping to modify activity within and among cells. "Critical future research should focus on finding proteins that target histone modifications to genetic regions with particular sequences," Dr. Zhang emphasized.

Jim Bono | EurekAlert!
Further information:
http://www.cshl.edu
http://www.nature.com/ng/journal/v40/n7/full/ng.154.html

Further reports about: Cell DNA Histone Zhang activity

More articles from Life Sciences:

nachricht Colorectal cancer risk factors decrypted
13.07.2018 | Max-Planck-Institut für Stoffwechselforschung

nachricht Algae Have Land Genes
13.07.2018 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Research finds new molecular structures in boron-based nanoclusters

13.07.2018 | Materials Sciences

Algae Have Land Genes

13.07.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>