Conaway Lab Demonstrates Mechanism by which Transcription Factor Controls Gene Expression

The paper, “YY1 functions with INO80 to activate transcription,” was posted to the Web site of Nature Structural & Molecular Biology on Aug. 26. It describes data showing that transcription factor YY1 works with a chromatin remodeling complex INO80.

“The paper offers the first demonstration of several interesting principles,” said Dr. Joan Conaway. “We learned that there is a role of the INO80 complex in gene regulation; that a chromatin remodeling complex plays a role as a coactivator for YY1; and that a transcription factor may travel with the remodeling complex required for it to gain access to promoters — suggesting that an initiating event in YY1-dependent gene activation is the corecruitment of YY1 and the human INO80 chromatin remodeling complex.”

YY1 is known to be important for turning “on” and “off” a significant number of genes, including genes that control cell division, cell differentiation, and development. Because of these contributions to cell cycle control, YY1 may eventually prove to be a good target for cancer therapy — but only if more can be learned about its functional mechanism.

“One of the most interesting findings in this paper is that one way YY1 controls gene expression is to bring the INO80 chromatin remodeling complex to the DNA sequences that control when a gene is turned on or off,” said Dr. Ron Conaway. “This process can make the gene available, or not, to the machinery that copies DNA into messenger RNA, which in turn directs the cell to make proteins.”

“This research is important because it illustrates that YY1 represents a switch point for modifying the activity of genes,” said Robb Krumlauf, Ph.D., Scientific Director. “We know that YY1 plays a significant role in regulating cellular processes, but this work from the Conaway Lab skillfully addresses questions about its mechanism of action, and provides a wealth of new information about an important transcription factor.”

Additional contributing authors from the Stowers Institute include Tingting Yao, Ph.D., Postdoctoral Research Fellow; Aaron Gottschalk, Predoctoral Researcher; Selene Swanson, Ph.D., Research Specialist II; Michael Washburn, Ph.D., Director of Proteomics; and Laurence Florens, Ph.D., Managing Director of Proteomics.

Contributing authors form the Department of Pathology at Harvard Medical School are Su Wu, Research Assistant Graduate Student; and Yang Shi, Ph.D., Professor of Pathology.

Drs. Conway hold faculty appointments in the Department of Biochemistry and Molecular Biology at the University of Kansas Medical Center. Dr. Joan Conaway was awarded the Helen Nelson Distinguished Chair by the Helen Nelson Medical Research Fund at the Greater Kansas City Community Foundation in 2005. More information about the Conaway Lab is available at www.stowers-institute.org/labs/ConawayLab.asp.

About the Stowers Institute
Housed in a 600,000 square-foot state-of-the-art facility on a 10-acre campus in the heart of Kansas City, Missouri, the Stowers Institute for Medical Research conducts basic research on fundamental processes of cellular life. Through its commitment to collaborative research and the use of cutting-edge technology, the Institute seeks more effective means of preventing and curing disease. The Institute was founded by Jim and Virginia Stowers, two cancer survivors who have created combined endowments of $2 billion in support of basic research of the highest quality.