Ali Shilatifard, Ph.D., Investigator, has identified a cellular factor that can reverse histone trimethylation caused by the trithorax gene, the Drosophila homologue of the human mixed lineage leukemia gene, MLL. MLL, which is found in translocations in a variety of hematological malignancies, is a histone H3K4 methyltransferase.

The paper, "The trithorax-group gene little imaginal discs in Drosophila encodes a histone H3 trimethyl-Lys4 demethylase," was posted in the Advanced Online Publication section of Nature Structural & Molecular Biology. The publication identified a cellular factor that can reverse histone trimethylation associated with mixed lineage leukemia. This, in turn, may allow for the identification of new targets for the treatment of leukemia caused by MLL translocations.

"This work demonstrates that a Drosophila gene product, little imaginal discs (Lid), removes methyl groups from histone H3K4," explains Dr. Shilatifard. "A reduction of Lid results in a specific genome-wide increase in H3K4 trimethylation levels with no effect on other patterns of histone trimethylations. Animals with reduced Lid levels have higher levels of H3K4 trimethylation, resulting in altered distribution of the chromo-helicase protein, the CHD1."

"Dr. Shilatifard's first publication since joining the Institute earlier this year is a fascinating one," said Robb Krumlauf, Ph.D., Scientific Director. "The role of MLL in a variety of blood-related cancers has been well-established. These findings give us a promising option for developing targeted treatments to combat these types of leukemia."



Additional contributing authors to the paper include co-equal first authors Joel Eissenberg, Saint Louis University School of Medicine, and Min Gyu Lee, The Wistar Institute; Jessica Schneider and Anne Ilvarsonn at Saint Louis University School of Medicine; and Ramin Shiekhattar, The Wistar Institute.

Dr. Shilatifard conducted some of this research prior to joining the Stowers Institute while serving as a faculty member of the Saint Louis University School of Medicine and the Saint Louis University Cancer Center.

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.

Contact: Marie Jennings
Stowers Institute for Medical Research