New findings from Rockefeller University researchers could guide the development of potent combination therapies that deliver more effective and durable treatment of leukemia. In work published online on March 1, 2017 in Nature, the scientists show that it’s possible to deactivate cellular programs involved in tumor growth by disrupting a protein that regulates genes. The article is titled “ENL Links Histone Acetylation to Oncogenic Gene Expression in Acute Myeloid Leukaemia.” At the center of this research are proteins called histones, which provide a physical support structure for the genome, and can also help regulate gene expression. Chemical modifications to histones can turn nearby genes on or off, and the cell interprets these chemical marks with the help of a variety of “reader” proteins. Once they recognize and bind to the chemically modified histones, the reader proteins recruit other factors that coordinate gene activation or inhibition. This process can become derailed in cancer, and drugs that selectively inhibit a class of readers known as BET proteins have already shown early promise in treating certain tumors. Now, a multi-institutional research team—led in part by Dr. David Allis, Joy and Jack Fishman Professor and Head of the Laboratory of Chromatin Biology and Epigenetics—has uncovered similar therapeutic potential for another, recently-identified class of reader proteins. These proteins share a structural feature called a YEATS domain, which specifically recognizes histones modified with a type of chemical mark called an acetyl group. “The functional importance of this reading activity by the YEATS domain was unknown,” says Dr. Liling Wan, a postdoctoral fellow in the Allis lab and lead author on the study, but she also notes strong evidence linking these proteins to cancer.
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