Corporate Banner
Satellite Banner
RNAi
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Possible Role for Huntington’s Gene Discovered

Published: Wednesday, January 16, 2013
Last Updated: Wednesday, January 16, 2013
Bookmark and Share
Mutant forms of the gene disrupt chemical modifications that control access to genes necessary for normal brain cell function.

About 20 years ago, scientists discovered the gene that causes Huntington’s disease, a fatal neurodegenerative disorder that affects about 30,000 Americans. The mutant form of the gene has many extra DNA repeats in the middle of the gene, but scientists have yet to determine how that extra length produces Huntington’s symptoms.

In a new step toward answering that question, MIT biological engineers have found that the protein encoded by this mutant gene alters patterns of chemical modifications of DNA. This type of modification, known as methylation, controls whether genes are turned on or off at any given time.

The mutant form of this protein, dubbed “huntingtin,” appears to specifically target genes involved in brain cell function. Disruptions in the expression of these genes could account for the neurodegenerative symptoms seen in Huntington’s disease, including early changes in cognition, says Ernest Fraenkel, an associate professor of biological engineering at MIT.

Fraenkel’s lab is now investigating the details of how methylation might drive those symptoms, with an eye toward developing potential new treatments. “One could imagine that if we can figure out, in more mechanistic detail, what’s causing these changes in methylation, we might be able to block this process and restore normal levels of transcription early on in the patients,” says Fraenkel, senior author of a paper describing the findings in this week’s issue of the Proceedings of the National Academy of Sciences.

Lead author of the paper is Christopher Ng, an MIT graduate student in biological engineering. Other authors are MIT postdoc Ferah Yildirim; recent graduates Yoon Sing Yap, Patricio Velez and Adam Labadorf; technical assistants Simona Dalin and Bryan Matthews; and David Housman, the Virginia and D.K. Ludwig Professor of Biology.

Unexpected patterns

DNA methylation has a major impact on genetic expression: Genes that are methylated at particular sites are usually dormant, because the methyl groups deny access to the proteins needed to copy DNA’s instructions and carry them to the rest of the cell. For a long time, scientists believed that DNA methylation patterns changed during embryonic development and then remained constant in adulthood. However, DNA methylation is emerging as important to a wide range of normal cell activity.

In the new study, the MIT team measured changes in methylation patterns during early stages of Huntington’s disease in cells derived from a brain region called the striatum in mouse embryos. This region, where planning of movement occurs, is severely affected by Huntington’s disease.

“We’re very interested in the earliest phases, because that’s when there’s the most hope that you could either slow down or stop progression of the disease, and allow people to live healthy lives much longer,” Fraenkel says. “By the time there is much more severe neurodegeneration, it’s unlikely that you’re going to be able to reverse the damage.”

Fraenkel and Ng were surprised to find a dramatic difference in methylation patterns between cells with normal and mutant forms of the huntingtin protein. Some genomic sites gained methylation, while others lost it. Many of the affected sites were in regions that regulate the expression of nearby genes necessary for neuron growth and survival.

Turning genes off and on

After observing the changing methylation patterns, the MIT team identified many proteins that tend to bind to the DNA sites where those changes take place. These proteins include Sox2 and others known to regulate genes involved in neuronal activity, including growth of the neurons.

The new findings go a long way toward explaining how the extra DNA repeats in the mutant form of the huntingtin gene might bring about disease, says Mark Mehler, a professor of neurology at the Albert Einstein College of Medicine. “People have not had a good sense, until this paper, of what these repeats might be doing,” says Mehler, who was not part of the research team. “What this study has done is demonstrated a mechanism by which expanded repeats can alter gene expression.”

The researchers are now studying whether huntingtin affects other modifications of DNA and histones, the proteins around which DNA is wound. Together, these might cause genes to be turned on or off inappropriately, Fraenkel says.

The researchers are also working with mouse models at different stages of Huntington’s disease to track how the methylation patterns change as the disease progresses. “That also gives us an opportunity to do interventions and test whether affecting particular proteins influences the progression of the disease,” Fraenkel says.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 4,000+ scientific posters on ePosters
  • More than 5,300+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Capsule Achieves Long-Term Drug Delivery
Novel drug delivery method could aid in elimination of malaria and treatment of many other diseases.
Monday, November 21, 2016
Predicting Cancer Cells’ Response to Chemotherapy
Researcher develop method for testing cell ability to perform different types of DNA repair, which can reveal tumors’ sensitivity to drugs.
Wednesday, November 02, 2016
Fighting Cancer with the Power of Immunity
Researchers at MIT have used a combination of four different therapies to activate both of the immune system’s two branches, producing a coordinated attack that led to the complete disappearance of large, aggressive tumors in mice.
Friday, October 28, 2016
Fighting Cancer with Immune Response
New treatment elicits two-pronged immune response that destroys tumors in mice.
Tuesday, October 25, 2016
Nanosensors Could Determine Tumours’ Ability to Remodel Tissue
Researchers design nanosensors that can profile tumours, focusing on protease levels.
Thursday, September 29, 2016
High-Capacity Nanoparticles
New type of nanoparticle can now have three or more drugs packaged within it, allowing for customised cancer therapy.
Thursday, September 15, 2016
Delivering Beneficial Bacteria
Method that transports microbes through the stomach to the intestine may benefit human health.
Thursday, September 15, 2016
Linking RNA Structure and Function
Biologists have deciphered a lncRNA structure and used the information to investigate its cellular protein interactions.
Friday, September 09, 2016
Triple-Action Therapy Patch Shows Promise
Patch that delivers drug, gene, and light-based therapy to tumor sites shows promising results in mice.
Wednesday, July 27, 2016
New Device can Study Electric Field Cancer Therapy
Microfluidic device allows study of electric field cancer therapy through low-intensity fields, preventing malignant cells spreading.
Friday, July 08, 2016
Long-Term Drug Release
New tablet attaches to the lining of the GI tract, resists being pulled away.
Thursday, April 07, 2016
Cancer Cells Remodel Environments Before Spreading
Researchers at MIT have found that the cancer cells remodel their environment to make it easier to reach nearby blood vessels.
Wednesday, March 16, 2016
Paving the Way for Metastasis
Cancer cells remodel their environment to make it easier to reach nearby blood vessels.
Tuesday, March 15, 2016
Curing Disease by Repairing Faulty Genes
New delivery method boosts efficiency of CRISPR genome-editing system.
Wednesday, February 03, 2016
No More Insulin Injections?
Encapsulated pancreatic cells offer possible new diabetes treatment.
Tuesday, January 26, 2016
Scientific News
Cancer Genetics: Key to Diagnosis, Therapy
When applied judiciously, cancer genetics directs caregivers to the right drug at the right time, while sparing patients of unnecessary or harmful treatments.
New Mechanism to Control Human Viral Infections Discovered
Researchers discover long sought after mechanism in human cells that could help treat diseases caused by viruses.
Study Reveals New Role for Hippo Pathway in Suppressing Cancer Immunity
Hippo pathway signaling regulates organ size by moderating cell growth, apoptosis and stem cell renewal, but dysregulation contributes to cancer development.
RNAi Activated in Response to Influenza
Discovery could lead to better ways of combating serious infections, including Ebola and Zika.
Gene Therapy Maintains Clotting Factor for Hemophilia Patients
Following a single gene therapy dose, the highest levels of an essential blood clotting factor IX were observed in hemophilia B patients.
Transporting Microscopic Cargo Between Human Cells
Scientists have developed a virus-inspired delivery system for material transport between cells.
Improving Drug Production with Computer Model
A model has been developed that can be used to improve and accelerate the production of biotherapeutics, cancer drugs, and vaccines.
Turning Off Asthma Attacks
Researchers discover a critical cellular “off” switch for the inflammatory immune response that causes asthma attacks.
New Strategy May Drop Cancer’s Guard
Scientists eye ways to deconstruct tumors’ protective wall with current diabetes drug.
Scientists Identify Unique Genomic Features in Testicular Cancer
The findings may shed light on factors in other cancers that influence their sensitivity to chemotherapy.
SELECTBIO

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
4,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,300+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!