Epigenetics, DNA and histone (arginine and lysine) methylation, DNA base flipping.

Design inhibitors of biological methylation: Enzymes that covalently modify histones control many cellular processes by affecting gene expression. A new class of these enzymes is the histone lysine methyltransferase (MTase) family, whose catalytic activity lies within a conserved domain, the SET domain. There has been evidence for a connection between SET-domain-containing proteins and cancer and that deregulation of SET-domain function has an important role in carcinogenesis.

Recently, we used elegant structural and biochemical analyses that provide insights into the long-standing question of how imprinted genes are targeted for DNA methylation (Jia et al, Nature 449, 248-251, 2007; Ooi et al, Nature 448, 714-717, 2007; Lan et al, Nature 448, 718-22, 2007). This revealed a novel mechanism of converting patterns of histone methylation into patterns of DNA methylation that mediate the heritable silencing, and the underlying DNA sequences of imprinted genes that contribute to the establishment of heritable methylation patterns.

Because of the vision and the support of the Georgia Research Alliance for creating a productive environment for research, education, and eventually the economic growth in Georgia.