Kansas City, Mo. (August 13, 2009) – The Stowers Institute’s Shilatifard Lab has applied a novel screen to improve our understanding of the molecular machinery required for the modification of histones — the primary component of chromatin. Their findings provide insights into the mechanisms underlying the onset of blood-related cancers.

     The work, conducted in collaboration with Michael Kobor, Ph.D., University of British Columbia, and Sue Jaspersen, Ph.D., Stowers Institute Assistant Investigator, is described in a “Immediate Early Publication” in today’s issue of Molecular Cell.

     The team investigated the function of the enzyme Disruptor-of-Telomeric-Silencing-1 (Dot1). Dot1 is capable of adding a methyl group to histone H3 on lysine 79 (H3K79) in a process called methylation. Abnormal H3K79 methylation has been linked to the onset of blood-related cancers.

     Several residues within the histone tails and some within the histone core can be altered by post-translation modifications, including methylation. Although the link between histone methylation by Dot1 and blood cancers is well established, very little is known about the molecular machinery required for H3K79 methylation.

     The project is the first to establish a connection between chromatin modification and the cell cycle.

     “We wanted to learn more about the molecular factors required for histone H3K79 methylation,” said Ali Shilatifard, Ph.D., Investigator and senior author on the paper. “We took advantage of a novel screen developed in our lab, and used budding yeast to dissect the molecular machinery required for Dot1’s function. The result may ultimately contribute to better treatments for blood-related cancers because H3K79 methylation is associated with the pathogenesis of Acute Myeloid Leukemia. Learning more about this process will help us in the development of targeted therapies.”

     Additional contributing authors include Julia Shulze, University of British Columbia; Jessica Jackson, Washington University School of Medicine; Shima Nakanishi, Ph.D., Postdoctoral Research Fellow; Jennifer Gardner, Research Technician II; Thomas Hentrich, Simon Fraser University; Jeff Haug, Managing Director, Cytometry Facility; and Mark Johnston, Ph.D., Washington University School of Medicine.

     Ali Shilatifard, Ph.D., Investigator, joined the Stowers Institute in 2007 from the Saint Louis University School of Medicine. Learn more about his work at www.stowers.org/labs/ShilatifardLab.asp. Sue Jaspersen, Ph.D., Assistant Investigator, also is an Assistant Professor in the Department of Molecular & Integrative Physiology at The University of Kansas School of Medicine. Learn more about her work at www.stowers.org/labs/JaspersenLab.asp.

About the Stowers Institute for Medical Research
     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, treating, and curing disease. Jim and Virginia Stowers endowed the Institute with gifts totaling $2 billion. The endowment resides in a large cash reserve and in substantial ownership of American Century Investments, a privately held mutual fund company that represents exceptional value for the Institute’s future.