|
Scientists Identify Key Roadblock to Gene Expression
May 09, 2008A team of scientists has provided, for the first time, a detailed map of how the building blocks of chromosomes, the cellular structures that contain genes, are organized in the fruit fly Drosophila melanogaster. The work identifies a critical stop sign for transcription, the first step in gene expression, and has implications for understanding how the AIDS virus regulates its genes. The findings will be published in the 15 May 2008 issue of the journal Nature.
The scientists found that nucleosomes--chromosomal building blocks made up of proteins around which DNA is coiled--occur at precise locations along genes that are actively undergoing transcription. They also showed that RNA polymerase--the enzyme that reads genes as the first step in making proteins--is stopped at the first nucleosome, where it remains idle until it is directed to continue moving forward. "This discovery is important because nucleosomes are barriers to transcription and we now are seeing the impact of nucleosome organization on RNA polymerase," said lead investigator B. Franklin Pugh, professor and Willaman Chair in Molecular Biology at Penn State University.
Using state-of-the-art ChIP-sequencing, a genome-mapping tool provided by collaborator Stephen S. Schuster, Penn State professor of biochemistry and molecular biology, and computational predictions developed by collaborators Ilya Ioshikhes, an assistant professor at Ohio State University, and Istvan Albert, a research assistant professor of bioinformatics at Penn State, the scientists precisely mapped the locations of hundreds of thousands of nucleosomes. The scientists then compared these maps to the team's earlier maps of the baker's yeast Saccharomyces cerevisiae, revealing that evolution has organized nucleosomes differently in simple life forms compared to more complex organisms like the fruit fly.
In yeast, a nucleosome sits on top of the transcription start site, so RNA polymerase must contend with that nucleosome as soon as it begins to transcribe the gene. In contrast, nucleosomes are positioned further downstream in fruit flies, so transcription starts but then soon pauses at the first nucleosome the RNA polymerase encounters. "This pause is maintained until chemical signals from the cell cue the removal of the nucleosome and encourage the RNA polymerase to continue along its path," said key collaborator David S. Gilmour, professor of molecular and cellular biology at Penn State and an expert on the pausing of RNA polymerase.
"A year ago, we could name about 10 genes that work this way. Now, we know of 1,000 in flies alone and we suspect there could be many more in humans," said Gilmour. "Even HIV genes have a paused RNA polymerase. Release of this pause may be key to activating HIV replication of otherwise latent viruses. Taking advantage of this new understanding might enable the development of more effective anti-viral drugs," he said.
"The bottom line is that we need to know how the expression of genes is regulated in order to understand the underpinnings of most human diseases, and these findings take us one step closer," said Pugh.
This work was funded by the National Institutes of Health and Penn State. More information about this project and others is on the Web at http://atlas.bx.psu.edu/
Penn State University
In yeast, a nucleosome sits on top of the transcription start site, so RNA polymerase must contend with that nucleosome as soon as it begins to transcribe the gene. In contrast, nucleosomes are positioned further downstream in fruit flies, so transcription starts but then soon pauses at the first nucleosome the RNA polymerase encounters. "This pause is maintained until chemical signals from the cell cue the removal of the nucleosome and encourage the RNA polymerase to continue along its path," said key collaborator David S. Gilmour, professor of molecular and cellular biology at Penn State and an expert on the pausing of RNA polymerase.
"A year ago, we could name about 10 genes that work this way. Now, we know of 1,000 in flies alone and we suspect there could be many more in humans," said Gilmour. "Even HIV genes have a paused RNA polymerase. Release of this pause may be key to activating HIV replication of otherwise latent viruses. Taking advantage of this new understanding might enable the development of more effective anti-viral drugs," he said.
"The bottom line is that we need to know how the expression of genes is regulated in order to understand the underpinnings of most human diseases, and these findings take us one step closer," said Pugh.
This work was funded by the National Institutes of Health and Penn State. More information about this project and others is on the Web at http://atlas.bx.psu.edu/
Penn State University
Polymerase News and Current Polymerase Events RSSDNA fingerprinting simplified
Agarose gel electrophoresis" Most teenagers wouldn't have a clue what this scientific term means, but middle school student Andrew Trigiano knows the protocol inside and out. When Andrew was 12, his father Robert Trigiano, a professor at the University of Tennessee, was looking for an interesting science project for his son.
Getting wise to the influenza virus' tricks
Influenza is currently a grave concern for governments and health organisations around the world. The worry is the potential for highly virulent bird flu strains, such as H5N1, to develop the ability to infect humans easily. New drugs and vaccines to halt the spread of the virus are badly needed.
Cancer could return unless stored ovarian tissue undergoes adequate testing before re-implantation
Cancer patients who have been successfully treated for their disease face the prospect of its return if stored ovarian (or testicular) tissue is transplanted back into their bodies without adequate checks, according to researchers at two university hospitals in Israel.
MRSA in hospital intensive care -- what's growing where?
Researchers are finding out which bugs grow in intensive care units to develop a novel sampling regime that would indicate the threat of MRSA and other superbugs in the environment, scientists heard today (Monday 31 March 2008) at the Society for General Microbiology's 162nd meeting being held this week at the Edinburgh International Conference Centre.
Biosensing nanodevice to revolutionize health screenings
One day soon a biosensing nanodevice developed by Arizona State University researcher Wayne Frasch may eliminate long lines at airport security checkpoints and revolutionize health screenings for diseases like anthrax, cancer and antibiotic resistant Staphylococcus aureus (MRSA).
Damaged veins heal faster with heparin treatment, laboratory study finds
A commonly used medication that prevents blood clots from forming may also prevent existing clots from damaging delicate vein walls - and may accelerate healing in a clot-damaged area of vein wall, according to new research from the University of Michigan Cardiovascular Center.
Toxins in cigarette smoke prevent stem cells from becoming cartilage
A toxic pollutant spread by oil spills, forest fires and car exhaust is also present in cigarette smoke, and may represent a second way in which smoking delays bone healing, according to research presented today at the annual meeting of the Orthopaedic Research Society in San Francisco.
New Test for Joint Infection Could Spare Some Patients an Unnecessary Procedure
A potential diagnostic test that could help surgeons confirm or rule out the presence of infection-causing bacteria in prosthetic joints that require surgical revision has been developed by researchers at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the National Institutes of Health (NIH).
Who found some new mechanisms of HBV virulence?
This dreadful HBV is small in size. The genome of this virus is a partial double stranded circle. When made fully double stranded, this genome carries about 3000 base pairs, compared to 200 kilo base pairs of the genome of the smallpox virus.
Stanford researchers make first direct observation of 3-D molecule folding in real time
All the crucial proteins in our bodies must fold into complex shapes to do their jobs. These snarled molecules grip other molecules to move them around, to speed up important chemical reactions or to grab onto our genes, turning them "on" and "off" to affect which proteins our cells make.
More Polymerase News Articles
| © 2008 BrightSurf.com |