Description:

The Department of Biochemistry and Molecular Genetics Departmental Seminar Series presents:

Johnathan R. Whetstine, PhD
Tepper Family MGH Research Scholar
Associate Professor of Medicine
Harvard Medical School and Massachusetts General Hospital Cancer Center

DNA copy gains and amplifications are often associated with tumorigenesis, poor prognosis and drug resistance. However, little is known about how these regions of the genome are selected for amplification. Our group discovered that modulation of epigenetic factors and their associated chromatin states control DNA copy gains of drug resistant regions. In fact, transient site-specific copy number gains occur in both normal and cancer cells upon manipulation of a histone H3 lysine 9/36 (H3K9/36) tri-demethylase KDM4A. However, the mechanism by which KDM4A is targeted to specific genomic regions and whether additional chromatin regulators are involved in this process were unknown. To begin addressing these questions, we performed a series of unbiased screens that uncovered insights about how KDM4A targeting influences DNA amplification in the human genome. We also demonstrated that specific epigenetic factors are working as a network to modulate DNA amplification of drug resistant regions of the genome. Furthermore, we uncovered KDM4A-independent DNA amplifications, which established that additional regions are undergoing epigenetic control for amplification. These currently unpublished data will be discussed at the seminar.