Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Finding the Sweet Spot

19.12.2011
Modifications to chromosomal proteins help ensure that brain-specific sugars are produced only in the appropriate tissues.

Many proteins are adorned with carbohydrate chains called glycans that can dramatically alter their stability, localization or function. These diverse sugars are assembled and modified by a variety of glycosylating enzymes, with some glycans exclusively manufactured within specific organs or tissues.


Figure 1: Neural cell-specific modifications to chromosomal proteins govern the production of Gnt-IX and thereby ensure that branched O-mannose glycan production is restricted to these cells.
Copyright : 2011 iStockphoto/sitox

The â1,6-branched O-mannosyl glycan appears only in the mammalian brain. Naoyuki Taniguchi’s team at the RIKEN Advanced Science Institute in Wako recently characterized the enzyme, N-acetylglucosaminyltransferase IX (GnT-IX, also called GnT-Vb) that produces this particular glycan variant1 (Fig. 1). “We knew that some glycan-synthesizing enzymes are expressed in restricted tissues, but did not know how they are expressed,” says Yasuhiko Kizuka, a researcher in Taniguchi’s laboratory. “This led us to investigate how GnT-IX is specifically expressed in the brain.”

Many genes are regulated by so-called ‘epigenetic mechanisms’, in which gene expression is modulated via modification of the histone protein scaffold that supports chromosomal DNA, and the researchers began by examining this possibility. When histone proteins undergo a modification known as acetylation, nearby genes are typically activated; conversely, removal of this acetylation has an inhibitory effect.

Taniguchi and colleagues determined that the gene encoding GnT-IX is typically maintained in an inactive, non-acetylated state in 3T3-L1, a cell line derived from the fibroblasts that form connective tissue. However, when the researchers treated these cells with a drug that promotes histone acetylation, they strongly expressed GnT-IX. The brain tumor-derived Neuro2A cell line, however, naturally expresses high levels of GnT-IX. The researchers found that these cells normally maintain the chromatin near this gene in a state that stimulates activation.

In subsequent experiments, Kizuka and Taniguchi not only identified specific DNA sequences that directly regulate GnT-IX activity, but also two proteins that bind to these sites to drive expression. They found one of these factors, CTCF, in both 3T3-L1 and Neuro2A cells, but its recruitment to the GnT-IX gene was far stronger under the favorable histone modification conditions found in the latter cells.

Intriguingly, a preliminary screen of four other glycosylation enzymes suggested that similar mechanisms govern their tissue-specificity. “Our work suggests that expression of many other glyco-genes could be regulated epigenetically,” says Kizuka.

In future studies, the researchers intend to explore how this regulatory mechanism plays into the bigger picture of glycan function. “Our group has been trying to elucidate the ‘glycan cycle’—how glycans are dynamically synthesized, play diverse roles and are degraded—using a systems biology approach,” says Kizuka. “This work tells us that epigenetic regulation is a part of this cycle.”

The corresponding author for this highlight is based at the System Glycobiology Research Group, RIKEN Advanced Science Institute

gro-pr | Research asia research news
Further information:
http://www.riken.jp
http://www.researchsea.com

More articles from Life Sciences:

nachricht Scientists enlist engineered protein to battle the MERS virus
22.05.2017 | University of Toronto

nachricht Insight into enzyme's 3-D structure could cut biofuel costs
19.05.2017 | DOE/Los Alamos National Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

Im Focus: Bacteria harness the lotus effect to protect themselves

Biofilms: Researchers find the causes of water-repelling properties

Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...

Im Focus: Hydrogen Bonds Directly Detected for the First Time

For the first time, scientists have succeeded in studying the strength of hydrogen bonds in a single molecule using an atomic force microscope. Researchers from the University of Basel’s Swiss Nanoscience Institute network have reported the results in the journal Science Advances.

Hydrogen is the most common element in the universe and is an integral part of almost all organic compounds. Molecules and sections of macromolecules are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

Innovation 4.0: Shaping a humane fourth industrial revolution

17.05.2017 | Event News

Media accreditation opens for historic year at European Health Forum Gastein

16.05.2017 | Event News

 
Latest News

New approach to revolutionize the production of molecular hydrogen

22.05.2017 | Materials Sciences

Scientists enlist engineered protein to battle the MERS virus

22.05.2017 | Life Sciences

Experts explain origins of topographic relief on Earth, Mars and Titan

22.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>