Exploring Networks of Epigenetic Enzymes

Every cell in the human body contains the same genetic information. However, expression of elements encoded in the DNA varies widely between different tissues. The expression profile of each cell is exquisitely regulated by various mechanisms collectively termed epigenetics. In general, epigenetic enzymes catalyze the selective addition or removal of chemical marks on chromatin, thereby altering the physical state of the DNA and recruitment of transcriptional machinery. Proper execution of these mechanisms is critical for normal cell function, and dysregulation can lead to various disease states. By studying the enzymes that govern epigenetic modification, we hope to identify targets and strategies for medicinal intervention in diseases such as cancer.

Uncovering the molecular networks surrounding histone demethylases

Lysine-specific histone demethylase 1A (KDM1A) is an epigenetic enzyme that has garnered much interests for its involvement in numerous disease states, notably breast cancer and leukemia. This enzyme removes methyls marks from histone proteins in chromatin and is classically believed to reduce expression of the affected genes. However, growing evidence indicates that association of KDM1A with discreet multiprotein complexes determines its ultimate effect on gene expression.  We seek to characterize these critical interactions through biochemical analysis (Jon Burg, Jen Link, Meghan Lawler), molecular cell biology (Jen Link), and proteomics (Jon Burg, Meghan Lawler).