|
A detailed map of how the building blocks of chromosomes are organized in the fruit fly Drosophila melanogaster identifies a critical stop sign for transcription, the first step in gene expression. The map has implications for understanding how the AIDS virus regulates its genes.
Scientists at Penn State University 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, 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.
The findings were published in the May 15, 2008 issue of the journal Nature.
Release Date: May 8, 2008
Source: 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 RNA polymerase encounters. Source: B. Franklin Pugh, Penn State
Filed Under: Drug Discovery
