Research into regulation of gene expression in fruit flies: Implications for AIDS

Several scientists have presented the first detailed map of how the building blocks of chromosomes, condensed areas of genes and DNA, are organised in the fruit fly Drosophila melanogaster. They have managed to identify a critical stop sign for transcription of genes. This work could lead to better understanding of how diseases, especially AIDS, regulate its genes.
In the fruit flies, the researchers found that nucleosomes, proteins which DNA is coiled around, occur at certain locations on genes which are being transcribed. RNA polymerase, the enzyme which reads the DNA strand, is stopped by the first nucleosome and it remains there until chemical signals from the cell cause the removal of the nucleosome and cue the RNA polymerase to continue. So nucleosomes are barriers for transcription and therefore the impact of nucleosome organisation on RNA polymerase can now be seen.
Using state of the art ChIP-sequencing, a genome mapping tool, researchers were able to map the locations of hundreds of thousands of nucleosomes. The researches then compared the fruit fly maps to earlier maps of the baker’s yeast Saccharomyces cerevisiae. This showed that evolution has organised nucleosomes differently in more complex organisms such as the fruit fly compared to simpler life forms like the baker’s yeast.
In the nucleosome organisation of the baker’s yeast the nucleosome sit on top of the transcription starting sites. This means that the nucleosome must be contended with before the RNA polymerase can start transcribing. In the fruit fly the nucleosome is further downstream, which allows the RNA polymerase to start transcribing until it reaches the nucleosome where it is paused. The RNA polymerase will stay idle until chemical signals from the cell cause the removal of the nucleosome from its path and encourage the RNA polymerase to continue transcribing. It has become known over the last year that the fruit fly has 1000 genes which work in this way and the researchers expect there are even more of these genes in humans.
HIV genes have paused RNA polymerase and releasing the pause may be key to activating HIV replication of otherwise dormant viruses. Better knowledge of how gene expression is regulated can lead to better understanding of most human diseases and development of new more effective anti-viral drugs and this research is another step towards completely understanding the regulation of gene expression.
For more info:http://www.sciencedaily.com­ /releases/2008/05/080508103623.htm

Penn State (2008, May 9). Key Roadblock To Gene Expression Identified: Implications For AIDS. ScienceDaily. Retrieved May 12, 2008, from http://www.sciencedaily.com­ /releases/2008/05/080508103623.htm