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UAMS Medical Center
UAMS Researchers Helping to Unlock a Protein Code
With Potential for Treating Disease
LITTLE ROCK – Molecular biologists at the University of Arkansas for Medical Sciences (UAMS) recently uncovered some of the first evidence for proteins that can read and write a “protein code,” providing a possible pathway to new treatments for diseases such as cancer at the genetic level.
Working with colleagues at The Rockefeller University in New York, UAMS researchers led by Alan Tackett, Ph.D., identified a member of a protein complex that appeared to “read” how other proteins are modified and react based on those modifications to “write” a subsequent modification – new genetic information.
The modified proteins – histones – are the “spools” around which is wrapped DNA – the chemical that carries the genetic information for all living organisms. The discovery of these protein interactions is believed to be key evidence in support of the “histone code hypothesis” maintaining that the histones provide additional genetic information when modified during diseases and other conditions. Tackett said the histone code helps explain how certain genes are turned on and off in a programmed manner through interactions between different types of proteins.
“If we can understand the histone code, we may be able to develop methods to regulate the protein modifications, with a long term goal of developing treatments for many diseases,” said Tackett, an assistant professor in the Department of Biochemistry and Molecular Biology of the UAMS College of Medicine and UAMS Graduate School.
The research is detailed in the article, “Yng1 PHD Finger Binding to Histone H3 Trimethylated at Lysine 4 Promotes NuA3 HAT Activity at Lysine 14 of H3 and Transcription at a Subset of Targeted ORFs,” that is published in the Dec. 8 issue of the journal Molecular Cell, a leading journal in the biological sciences.
Tackett corresponded on the article with David Allis, Ph.D., head of the Laboratory of Chromatin Biology at The Rockefeller University who is a pioneer in studying the histone code. The lead author of the article was Sean Taverna, Ph.D., of The Rockefeller University. Other UAMS researchers in the project included Heather Lavender, a research assistant in the Department of Biochemistry and Molecular Biology, and Lauren Blair, a graduate student in the Department of Biochemistry and Molecular Biology.
In the research, one part of a multi-protein complex,Yng1, was shown to interact with a modified histone called H3. Yng1 was found to be an “effector” protein since it recognized how H3 was modified and responded in a way that activated gene expression – writing additional histone code.
The researchers used a technique developed in part by Tackett called I-DIRT to uncover the cellular protein interactions with Yng1. The I-DIRT technology identifies the nature of protein interactions at the cellular level, Tackett said.
Key to the work performed by Tackett’s group was the analysis equipment in the UAMS Proteomics Facility. The facility is home to three mass spectrometers and robotic sampling equipment for analysis of proteins. The equipment allows quicker and more efficient protein analysis than was previously available.
The UAMS Proteomics Facility is associated with the Arkansas Cancer Research Center and the Department of Biochemistry and Molecular Biology in the UAMS College of Medicine and Graduate School. Funding for this facility was provided in part by the Arkansas Biosciences Institute through the state’s share of the nationwide tobacco settlement.