Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Penn Study Details Dimmer Switch for Regulating Cell's Read of DNA Code

Published: Wednesday, January 09, 2013
Last Updated: Wednesday, January 09, 2013
Bookmark and Share
Findings have implications for cancer and neurological treatments.

Epigenetics - the science of how gene activity can be altered without changes in the genetic code - plays a critical role in every aspect of life, from the differentiation of stem cells to the regulation of metabolism and growth of cancer cells. Epigenetic factors act by reworking the structure in which genes reside, called chromatin. Inside chromatin, DNA is wound around proteins called histones. Several new cancer treatments interfere with the function of enzymes that chemically mark the histones to alter the readout of the DNA code and ramp the expression of genes up or down, as if with a dimmer switch. Enzymes called histone deacetylases (HDACs) erase the mark and shut off gene expression.

A team led by Mitchell A. Lazar, M.D., Ph.D., director of the Institute for Diabetes, Obesity, and Metabolism at the Perelman School of Medicine, University of Pennsylvania, has been studying HDAC3 for several years. They discovered that the enzyme activity of HDAC3 requires interaction with a specific region on another protein, which they dubbed the Deacetylase Activating Domain or "DAD.” This “nuts and bolts” discovery on the epigenetic control of a person’s genome has implications for cancer and neurological treatments.

This domain is found only in proteins that are nuclear receptor corepressors (NCoR1 and NCOR2), which assist receptor proteins in the nucleus to downregulate gene expression.

The team showed that HDAC3 enzyme activity is undetectable in mice bearing mutations in the DAD of both NCOR1 and NCOR2, also called SMRT, despite having normal levels of HDAC3 protein. The findings were published this week in Nature Structural & Molecular Biology.

HDAC3 is required for normal mouse development and tissue-specific functions. In cell culture studies, the HDAC3 protein itself has minimal enzyme activity but gains its histone-deacetylation function from stable association with the DAD.

“We developed a unique mouse model to directly test whether HDAC3 absolutely requires NCOR1 and/or SMRT to be activated,” says Lazar. “The answer is yes.” The results clearly show that, although tissue levels of HDAC3 are normal in this mouse model, the protein does not have detectable enzyme activity in embryos and various tissues of the engineered mice.

Surprisingly, the engineered mice are born and live to adulthood, whereas genetic absence of HDAC3 is lethal to the mice before they are born.  This suggests that HDAC3 may have a deacetylase-independent function which, Lazar says, “is potentially of major importance, because HDAC inhibitors are currently used clinically to treat cancer, and are in clinical development for neurological illnesses and other disorders.  We are working hard in the lab to sort this out.”

Co-authors are Seo-Hee You, Hee-Woong Lim, Zheng Sun, Molly Broache, and Kyoung-Jae Won, all from Penn. The research was supported in part by the National Institute of Diabetes, and Digestive and Kidney Diseases (R37DK43806) and a Mentor Based Fellowship from the American Diabetes Association.


Further Information
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 2,500+ scientific posters on ePosters
  • More Than 3,700+ 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

Study Questions Presence in Blood of Heart-Healthy Molecules from Fish Oil Supplements
A new study from the Perelman School of Medicine at the University of Pennsylvania questions the relevance of fish oil-derived SPMs and their purported anti-inflammatory effects in humans.
Monday, August 03, 2015
Limber Lungs: One Type of Airway Cell Can Regenerate Another Lung Cell Type
Findings from animal study have implications for disorders such as chronic obstructive pulmonary disease.
Tuesday, April 14, 2015
New Approach to Promote Regeneration of Heart Tissue
Study in animal model paving way forward for tissue repair.
Thursday, March 19, 2015
Penn Researchers Tame the Inflammatory Response in Kidney Dialysis
Researchers temporarily suppress complement during dialysis to avoid these problems.
Saturday, December 13, 2014
First Atlas of Body Clock Gene Expression in Mammals Informs Timing of Drug Delivery
Penn Medicine study has implications for 100 top-selling US drugs, half of which target daily-oscillating genes.
Thursday, October 30, 2014
Study Identifies Potential Treatment Target for Cocaine Addiction
Small change in receptor subunit reduces cocaine seeking in an animal model of addiction.
Thursday, October 30, 2014
Funding for DNA Vaccines to Fight Infectious Disease
DARPA awards $12 million to Penn-led group to develop synthetic DNA vaccines to fight infectious disease.
Wednesday, October 22, 2014
Personalized Cellular Therapy Achieves Complete Remission in 90 Percent of ALL Patients Studied
University of Pennsylvania and Children's Hospital of Philadelphia studies reveal unprecedented results with investigational therapy made from patients' own immune cells.
Friday, October 17, 2014
Ovarian Cancer Oncogene Found in "Junk DNA"
The study is published online in this week in Cancer Cell.
Wednesday, September 10, 2014
Activating Pathway Could Restart Hair Growth in Dormant Hair Follicles
Manipulation of the Wnt/ß-catenin signaling pathway could provide therapeutic targets for hair loss, unwanted hair growth and skin cancer.
Tuesday, December 10, 2013
Researchers Identify Four New Genetic Risk Factors for Testicular Cancer
Large, first-of-its-kind study finds genomic regions associated with higher risk.
Wednesday, May 15, 2013
Newly Described Type of Immune Cell and T Cells Share Similar Path to Maturity
Better understanding of cells' development has implications in study of inflammatory diseases.
Wednesday, May 15, 2013
T-Cell Therapy Eradicates an Aggressive Leukemia in Two Children
CHOP/Penn Medicine oncology team reports complete remission in pediatric ALL patients.
Tuesday, March 26, 2013
Study Confirms No Transmission of Alzheimer's Proteins between Humans
No evidence to show that proteins can spread around within the brain or between animals and humans.
Wednesday, February 06, 2013
Recently Identified Immune Cells Possible Therapeutic Target for Eczema
The increasing incidence of allergic skin diseases have spurred researchers to look for better ways to control these immune system-based disorders.
Wednesday, February 06, 2013
Scientific News
The Changing Tides of the In Vitro Diagnostics Market
With the increasing focus in personalized medicine, diagnostics plays a crucial role in patient monitoring.
LaVision BioTec Reports on the Neuro Research on the Human Brain After Trauma
Company reports on the work of Dr Ali Ertürk from the Institute for Stroke and Dementia Research at LMU Munich.
NIH Study Shows No Benefit of Omega-3 Supplements for Cognitive Decline
Research was published in the Journal of the American Medical Association.
Less May Be More in Slowing Cholera Epidemics
Mathematical model shows more cases may be prevented and more lives saved when using one dose of cholera vaccine instead of recommended two doses.
Investigating the Vape
Expert independent review concludes that e-cigarettes have potential to help smokers quit.
NIH Launches Human RSV Study
Study aims to understand infection in healthy adults to aid development of RSV medicines, vaccines.
Researchers Discover Synthesis of a New Nanomaterial
Interdisciplinary team creates biocomposite for first time using physiological conditions.
Poor Survival Rates in Leukemia Linked to Persistent Genetic Mutations
For patients with an often-deadly form of leukemia, new research suggests that lingering cancer-related mutations – detected after initial treatment with chemotherapy – are associated with an increased risk of relapse and poor survival.
Flu Remedies Help Combat E. coli Bacteria
Physiologists from the University of Zurich have now discovered why the intestinal bacterium Escherichia coli (E. coli) multiplies heavily and has an inflammatory effect.
Marijuana Genome Unraveled
A study by Canadian researchers is providing a clearer picture of the evolutionary history and genetic organization of cannabis, a step that could have agricultural, medical and legal implications for this valuable crop.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
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
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!