Navigation Links
Powerful new method allows scientists to probe gene activation
Date:4/8/2010

NYU Langone Medical Center researchers have developed a powerful new method to investigate the discrete steps necessary to turn on individual genes and examine how the process goes wrong in cancer and other diseases. The finding, based on seven years of research and described in the April 9 issue of Molecular Cell, allows scientists to investigate the unfolding of DNA, a process required for gene activation.

"The new methodology allows us to examine the steps that turn on individual genes in order to figure out what part of the process breaks down in diseases like cancer, " says Danny Reinberg, PhD, professor of biochemistry at NYU Langone Medical Center and a Howard Hughes Medical Institute Investigator, who led the study. "Right now we have the book with a lot of chapters. The idea now is to read each of those chapters and analyze how things happen. After that, we can start devising assays to test for steps or molecules we want to target," says Dr. Reinberg, who has been studying the molecular processes governing how genetic information is transferred for more than 20 years. He is a leader in the field of epigenetics, which probes the modifications that control when genes are expressed, many of which are linked to a wide variety of diseases.

DNA, in its simplest form, is a long double-stranded helix. Inside the cell's nucleus, however, the helix is further twisted and wrapped around protein complexes to form much more compact fibers called chromatin. For example, chromosome 22, one of the smallest human chromosomes, would be about 1.5 centimeters long as a simple DNA helix, but twisted around the protein complexes, it is just two micrometers, a 10,000-fold compression.

However, the degree of compaction is dynamic and is part of the way cells control gene transcription. When a gene is inactive, its chromatin is packed together more tightly than when the gene is actively transcribed. Although scientists have known about these changes for years, they didn't know how the cell regulated the shift from the most highly compact fiber, which is 30 nanometers across (about the size of the tiniest particle of smoke from cooking oil), to the less compact one, which is just 11 nanometers. They wanted to understand the process, but faced a major hurdleno one knew how to recreate a 30 nanometer fiber in a test tube.

With their new study, Dr. Reinberg and his colleagues have cleared that hurdle, allowing the team to begin teasing apart the steps to unwind the fiber and start transcription in a test gene. "It was a lot of background work, but in the end we got a nice story that, I believe, is the only story out there that goes from highly compact chromatin to transcription," says Dr. Reinberg.

Once the fiber was in the assay tubes, the team found that a DNA regulatory protein called the retinoic acid receptor (RAR) could access its binding site on the DNA, even when the chromatin was in its most tightly wound state. When researchers added the hormone that stimulates RAR, called retinoic acid, a derivative of vitamin A, to the system, things started to change. . The hormone-bound RAR began to unwind the chromatin and move aside large protein complexes, called nucleosomes, to make room for other DNA unwinding proteins and transcription factors. As they added in more and more factors, the DNA continued to loosen up, until finally, the team could see transcription start from their test gene PEPCK, which is controlled by RAR.

Significantly, electron microscopy showed that the 30 nanometer fiber formed in the test tube resembles the one in cells. Moreover, as the team added individual factors to the system, they used biochemical assays, such as DNA cutting experiments, to show that the nucleosome movement mimicked what happens when the PEPCK gene is turned on by retinoic acid in living cells.


'/>"/>

Contact: Dorie Klissas
dorie.klissas@nyumc.org
212-404-3555
NYU Langone Medical Center / New York University School of Medicine
Source:Eurekalert

Related biology news :

1. Innovative Document Security Technology Proves Powerful in Avoiding Counterfeit Products
2. Powerful new molecular GPS helps probe aging and disease processes
3. Powerful nutrient cocktail can put kids with Crohns into remission
4. Changing climate likely to make super weed even more powerful
5. InVitria to Unveil Powerful Cell Culture Media Component ZAP-CHO
6. Collaboration leads to success: Most powerful computer of its kind in western N.Y. available worldwide
7. Cancer Genomics Browser gives cancer researchers a powerful new tool
8. Biologists learn structure, mechanism of powerful molecular motor in virus
9. Newly identified gene powerful predictor of colon cancer metastasis
10. Powerful online tool for protein analysis provided pro bono by Stanford geneticist
11. Apelin hormone injections powerfully lower blood sugar
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/31/2016)... , March 31, 2016  Genomics firm Nabsys has ... CEO, Barrett Bready , M.D., who returned to ... the original technical leadership team, including Chief Technology Officer, ... Product Development, Steve Nurnberg and Vice President of Software ... the company. Dr. Bready served as CEO ...
(Date:3/21/2016)... Massachusetts , March 22, 2016 ... facial recognition with passcodes for superior security   ... ), a leading provider of secure digital communications services, ... their biometric technology and offer enterprise customers, particularly those ... secure facial recognition and voice authentication within a mobile ...
(Date:3/14/2016)... March 14, 2016 NXTD ) ("NXT-ID" ... commerce market, announces the airing of a new series of ... week of March 21 st .  The commercials will air ... popular Squawk on the Street show. --> NXTD ... growing mobile commerce market, announces the airing of a new ...
Breaking Biology News(10 mins):
(Date:5/23/2016)... (PRWEB) , ... May 23, 2016 , ... ... That Will Drive Precision Farming in 2017 and Beyond. The paper outlines the ... in the precision ag industry. , “We’ve witnessed a lot of highs and ...
(Date:5/23/2016)... Palo Alto, CA (PRWEB) , ... May 23, ... ... tank and public interest organization focused on molecular nanotechnology, announced the winners for ... honor of pioneer physicist Richard Feynman, are given in two categories, one for ...
(Date:5/20/2016)... , ... May 20, 2016 , ... The recent recall ... as reported by Food Safety News on May 12, 2016(1), demonstrates the need for ... Olsen, CEO of Baltimore-based biotech firm, PathSensors, Inc. , PathSensor’s latest ...
(Date:5/19/2016)... Regen BioPharma, Inc ... announced today initiation of a preclinical development program ... cancer immunotherapeutic product leveraging its NR2F6 immunological checkpoint. ... generation of cord blood derived killer cells whose ... product in development will be a "universal donor" ...
Breaking Biology Technology: