Scientists identify key roadblock to gene expression

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/

CONTACTS:
B. Franklin Pugh: (+1) 814-863-8252,
David Gilmour: (+1) 814-863-8905,
Barbara Kennedy (PIO): (+1) 814-863-4682,

ILLUSTRATION:
A drawing that illustrates certain aspects of this research is on the Web at http://www.science.psu.edu/alert/Pugh5-2008.htm