(Press-News.org) Imagine being able to control genetic expression by flipping a light switch. Researchers at North Carolina State University are using light-activated molecules to turn gene expression on and off. Their method enables greater precision when studying gene function, and could lead to targeted therapies for diseases like cancer.
Triplex-forming oligonucleotides (TFOs) are commonly used molecules that can prevent gene transcription by binding to double-stranded DNA. NC State chemist Dr. Alex Deiters wanted to find a way to more precisely control TFOs, and by extension, the transcription of certain genes. So Deiters attached a light-activated "cage" to a TFO. When exposed to ultraviolet (UV) light, the cage is removed, and the TFO is free to bind with DNA, inhibiting transcription of the gene of interest.
"In the absence of light, transcription activity is 100 percent," says Deiters. "When we turn on the light, we can take it down to about 25 percent, which is a significant reduction in gene expression."
Additionally, Deiters fine-tuned the process by attaching a caged inhibitor strand to the TFO. In the absence of UV light, the TFO behaves normally, binding to DNA and preventing gene expression. However, when exposed to UV light, the caged inhibitor activates and stops the TFO from binding with DNA, turning gene transcription on.
"We've created a tool that allows for the light-activation of genetic transcription," Deiters says. "By giving researchers greater temporal and spatial control over gene expression, we've expanded their ability to study the behavior of particular genes in whichever environment they choose."
###The research appears online in ACS Chemical Biology, and was funded by the National Institutes of Health. Deiters worked with NC State graduate students Jeane M. Govan, Rajendra Uprety and James Hemphill and Wake Forest University's Mark O. Lively on the research.
Note to editors: An abstract of the paper follows.
"Regulation of Transcription through Light-Activation and Light-Deactivation of Triplex-Forming Oligonucleotides in Mammalian Cells"
Authors: Alexander Deiters, Jeane M. Govan, Rajendra Uprety, James Hemphill, North Carolina State University; Mark O. Lively, Wake Forest University School of Medicine
Published: ACS Chemical Biology
Abstract: Triplex-forming oligonucleotides (TFOs) are efficient tools to regulate gene expression through the inhibition of transcription. Here, nucleobase-caging technology was applied to the first temporal regulation of transcription through light-activated TFOs. Through site-specific incorporation of caged thymidine nucleotides, the TFO: DNA triplex formation is blocked, rendering the TFO inactive. However, after a brief UV irradiation, the caging groups are removed, activating the TFO and leading to the inhibition of gene transcription. Furthermore, the synthesis and site-specific incorporation of caged deoxycytidine nucleotides within TFO inhibitor sequences was developed and allows for the light-deactivation of TFO function and thus photochemical activation of gene expression. After UV-induced removal of the caging groups, the TFO forms a DNA dumbbell structure, rendering it inactive, releasing it from the DNA, and activating transcription. These are the first examples of light-regulated TFOs and their application in the photochemical activation and deactivation of gene expression. In addition, hairpin loop structures were found to significantly increase the efficacy of phosphodiester DNA-based TFOs in tissue culture.
Researchers use light to switch on gene expression
2012-05-11
ELSE PRESS RELEASES FROM THIS DATE:
OU researcher examines the healthy and unhealthy snack choices of fourth- and fifth-grade students
2012-05-11
A health nutrition education program to fight childhood obesity in America is a possible outcome of a study by a University of Oklahoma researcher and a colleague. The study looked at factors affecting a child's decision when choosing healthy or unhealthy snacks.
Paul Branscum, assistant professor, OU Department of Health and Exercise Science, College of Arts and Sciences, surveyed 167 fourth- and fifth-grade students in the Midwest to find out what snacks the students were eating between meals. Branscum asked the students to record their choices over a 24-hour-period.
Survey ...
Mechanistic discovery links psoriasis to increased risk of cardiovascular disease
2012-05-11
The link between psoriasis and cardiovascular events has been observed for years, however the mechanics were unknown. For the first time, Case Western Reserve University School of Medicine researchers have discovered preclinical evidence demonstrating that the inflammatory skin disease leads to cardiovascular disease. Further, the research demonstrated that aggressive reversal of psoriasis reduces the cardiovascular risk as well. Psoriasis is a chronic disease of the immune system that appears as raised, inflamed, scaly red patches of skin and is often associated with intense ...
University of Tennessee professor looks at how stars' endorsements can help -- or hurt -- politicians
2012-05-11
Actor George Clooney is planning a fundraising dinner to raise $10 million for President Barack Obama. Comedian Chelsea Handler and actor Tom Hanks are also Obama supporters.
Comedian Jeff Foxworthy, rocker Ted Nugent and country singer Trace Adkins have said they back the likely Republican nominee, Mitt Romney.
Star-studded endorsements may be attention grabbing, but does it influence voters?
Yes, it does, according to research recently published by a political scientist at the University of Tennessee, Knoxville.
Professor Anthony Nownes has found that celebrities ...
Establishing a threshold for surgery in recurrent acute rhinosinusitis
2012-05-11
Alexandria, VA — A study in the May 2012 issue of Otolaryngology–Head and Neck Surgery suggests a threshold for when to choose surgery over medical therapy for recurrent acute rhinosinusitis (RARS) based on the patients' lost productivity in response to RARS and each treatment strategy.
The authors compare the burden of surgery and the burden of disease. On one hand, "Surgery and postoperative convalescence for comprehensive endoscopic sinus surgery can take 5 to 7 days or 3 to 5 workdays…," they write. However, the impact of each bout of infection also diminishes quality ...
Screening for esophageal disease with unsedated transnasal endoscopy is safe and feasible
2012-05-11
OAK BROOK, Ill. – May 10, 2012 – Researchers report that unsedated transnasal endoscopy is a feasible, safe, and well-tolerated method to screen for esophageal disease in a primary care population. This study is the largest reported experience with transnasal endoscopy in the United States. The study appears in the May issue of GIE: Gastrointestinal Endoscopy, the monthly peer-reviewed scientific journal of the American Society for Gastrointestinal Endoscopy (ASGE).
Esophageal cancer is the most rapidly increasing type of neoplasia in terms of incidence in the United ...
Smoking ban reduced maternal smoking and preterm birth risk
2012-05-11
New Rochelle, NY, May 10, 2012—A citywide ban on public smoking in Colorado led to significant decreases in maternal smoking and preterm births, providing the first evidence in the U.S. that such interventions can impact maternal and fetal health, according to an article in Journal of Women's Health, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. The article is available free on the Journal of Women's Health website at http://www.liebertpub.com/jwh.
Prenatal exposure to tobacco smoke–whether the mother is a smoker or exposure is from environmental ...
Discovery in cell signaling could help fight against melanoma
2012-05-11
The human body does a great job of generating new cells to replace dead ones but it is not perfect. Cells need to communicate with or signal to each other to decide when to generate new cells. Communication or signaling errors in cells lead to uncontrolled cell growth and are the basis of many cancers.
At The University of Texas Health Science Center at Houston (UTHealth) Medical School, scientists have made a key discovery in cell signaling that is relevant to the fight against melanoma skin cancer and certain other fast-spreading tumors.
The scientists report that ...
Economic theory actually works in health care
2012-05-11
WASHINGTON – A study of 7,424 privately insured colon cancer patients found that managed care presence in the market and hospital competition increased the likelihood laparoscopic surgery to treat colon cancer lowered costs, a national team of researchers led by a professor at the George Washington University School of Public Health and Health Services reported in the journal Cancer, May 8, 2012.
Colon cancer is the second leading cause of cancer death in the U.S., and surgical resection is the standard of care. In 2004, there were approximately 134,000 colectomies performed ...
Research reveals novel transport mechanism for large ribonucleoproteins
2012-05-11
WORCESTER, Mass. — The movement of genetic materials, such as RNA and ribosomes, from the nucleus to the cytoplasm is a critical component in a cell's ability to make the proteins necessary for essential biological functions. Until now, it was believed the nuclear pore complex was the sole pathway between the cell nucleus and cytoplasm for these materials. New evidence published in Cell by Vivian Budnik, PhD, Melissa J. Moore, PhD, and colleagues at the University of Massachusetts Medical School, reveals a novel budding mechanism, similar to the process used by some viruses, ...
Long-lived rodents have high levels of brain-protecting factor
2012-05-11
SAN ANTONIO (May 10, 2012) — The typical naked mole rat lives 25 to 30 years, during which it shows little decline in activity, bone health, reproductive capacity and cognitive ability. What is the secret to this East African rodent's long, healthy life?
Scientists from the United States and Israel found a clue. From infancy to old age, naked mole rats are blessed with large amounts of a protein essential for normal brain function.
"Naked mole rats have the highest level of a growth factor called NRG-1 in the cerebellum. Its levels are sustained throughout their life, ...