Acetyltransferases are enzymes that introduce a new acetyl functional group into histone proteins, a process by which all chromosome functions are controlled.

The findings were posted to the Web site of Nature Structural and Molecular Biology yesterday and will appear in a future print edition of the journal.

ATAC is unique as the only acetyltransferase protein complex that contains two distinct acetyltransferase enzymes; one that generally activates processes like gene transcription and DNA repair and another that makes a specific modification thought to alter chromosome structure. ATAC can also assist in the movement of chromosome subunits, called nucleosomes, along DNA.

The work was conducted using the Drosophila, or fruit fly, model ” ATAC is present in multicellular organisms, including fruit flies and humans, but not in lower eukaryotes, like yeast.

We knew that the ATAC complex existed and that it was only present in multicellular organisms, but we did not know all the proteins it contained or what their functions were, said Tamaki Suganuma, Ph.D., Postdoctoral Research Associate and first author on the paper. In this work, we were able to identify the protein components of ATAC to gain insight into its functions.

The improved understanding of ATAC may lead to a better understanding of a number of human diseases.

We were able to show that in Drosophila, the ATAC complex is essential for development of the embryo to an adult organism, said Jerry Workman, Ph.D., Investigator and senior author on the publication. It is likely that ATAC will also be required for development of mammals, including humans, and that by understanding the functions of ATAC we will be better able to pinpoint its role in developmental defects and cancers. Having characterized all of the proteins in ATAC, the Workman Lab will now focus on which chromosomal functions it regulates and how these actions contribute to development.

stowers-institute/

"We discovered a clear differentiation between the metabolomic profiles of the Parkinson's disease patients versus those of the controls," Dr. Beal says. "No one molecule was definitive, but a pattern of about 160 compounds emerged that was highly specific to Parkinson's patients."

The significance of many individual compounds to the disease remains unknown and will be the focus of future study. But changes in a few well-known metabolites linked to oxidative stress were clearly linked to Parkinson's. These included low levels of the antioxidant uric acid; an increase in blood levels of another antioxidant, glutathione; and increased levels of a marker for oxidative damage called 8-OHdG.

"Together, these and other compounds were arranged into a metabolomic pattern that identified Parkinson's disease with great accuracy," Dr. Beal says.

He stressed that more work needs to be done to validate the finding, and a test that might be used routinely by doctors is still a few years away.

"We are currently enlarging the sample size and studying people at serial intervals, to see if this test might also serve as a benchmark for disease progression," Dr. Beal says. "We are also looking at people who carry a gene for a familial form of Parkinson's, but who do not have the illness now. We hope to track them over time to see if this metabolomic profile is predictive of disease onset."

If those data prove as promising as this early trial, an early-detection blood test for Parkinson's disease could someday become a reality. According to Dr. Beal, "That would be a big step forward for both the treatment and the study of this devastating illness."

medrnell/