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Workman Lab Publishes Findings on Chromosomal Proteins and Histones in Gene Transcription The findings, made in collaboration with colleagues at The Scripps Research Institute, were published in the Nov. 18, 2005 issue of the scientific journal Cell. Contributing authors from the Stowers Institute include Bing Li, Ph.D., Postdoctoral Research Associate; Laurence Florens, Ph.D., Managing Director of Proteomics; Tamaki Suganuma, Ph.D., Postdoctoral Research Associate; Selene K. Swanson, Research Specialist II; Kenneth K. Lee, Ph.D., Postdoctoral Research Associate; Wei-Jong Shia, Predoctoral Research Associate; and Michael P. Washburn, Ph.D., Director of Proteomics. When a gene is transcribed into ribonucleic acid (RNA) by RNA polymerases, that region of the chromosome is modified to facilitate polymerase reading of the sequence of the gene. This includes a process of acetylating histones, the building block proteins of the chromosome. However, when the histones on a gene are acetylated, the gene is in an open exposed state. This allows other polymerases to attach improperly to the middle of the gene and start transcription there, as opposed to the proper attachment at the beginning of the gene. Thus, acetylation of the gene needs to be reversed following its transcription. To ensure this, RNA polymerase carries with it another enzyme which methylates histones when the polymerase passes along the gene. The methylated histones are then recognized by another enzyme complex, called a deacetylase, which removes acetylation from histones on the gene and closes the gene so polymerases can not attach in the middle. “This was a discovery based project,” said Dr. Workman. “We sought to identify all the proteins associated with a histone deacetylase with the idea that they would provide clues as to what the enzyme is used for. These pieces of information and a few more from the scientific literature allowed us to model the function of these proteins and then test and prove it.” Inhibitors of histone deacetylases are currently being tested in clinical trials as promising anti-tumor drugs. Understanding the cellular functions that these inhibitors affect will be important to understand their anti-tumor activity and may lead to the development of more specific anti-tumor drugs in the future. “The Workman lab’s findings tell us something fundamental about the role of chromosomal proteins and histones in the process of gene transcription,” said Robb Krumlauf, Ph.D., Scientific Director. “When unacetylated they play a crucial role in protecting the body of a gene so that RNA polymerases only begin transcription at the correct place, the beginning of the gene.” More information about Dr. Workman’s lab group can be found at http://www.stowers-institute.org/labs/workmanLab.asp. About the Stowers Institute |
