In 2003, we published a landmark paper describing purification of the first mammalian histone H3-lysine 4-methyltransferase (H3K4MT) complexes (Mol Cell Biol 23:140, 2003). We have shown that these complexes contain either the H3K4MT MLL3 or its paralog MLL4 (PNAS 103:15392, 2006). Other groups have subsequently shown that these complexes also contain the H3K27-demethylase UTX. We have pioneered dissecting the physiological roles of these MLL3/UTX- and MLL4/UTX-complexes ever since.

These complexes are associated with two prominent human disorders. Somatic mutations of the MLL3, MLL4, and UTX genes in diverse human cancers uncovered their tumor suppressor function. Mutations in the MLL4 and UTX genes have been found to cause a devastating human congenital developmental disorder, named Kabuki syndrome, that affects many parts of the body.

Our current focus is on characterizing the roles of the MLL3/UTX- and MLL4/UTX-complexes in diverse metabolic processes (particularly in the newly emerging theme for interplays between diet and tumorigenesis). We also strive to define the genome-wide gene regulatory network of MLL4/UTX-complex underlying various developmental deficits in Kabuki syndrome.

 

Welcome to Jae Lee’s Lab

at OHSU, Portland, Oregon


Gene Regulation in Metabolism and Kabuki Syndrome