Mammalian SWI/SNF Enzymes Promote Cell Differentiation

Our research interests are focused on the biological functions of the mammalian SWI/SNF ATP-dependent chromatin remodeling enzymes.  This enzyme family uses ATP hydrolysis to break histone-DNA contacts and alter nucleosome structure and/or positioning.  My lab provided the first evidence that mammalian SWI/SNF enzymes remodel chromatin at endogenous gene loci, and we established that these SWI/SNF enzymes are essential for many tissue-differentiation events.  Our major efforts over the last ten years have centered on how SWI/SNF enzymes cooperate with tissue specific transcription factors and histone modifying enzymes to promote tissue-specific gene expression, with an emphasis on myogenesis and adipogenesis.  In particular, we have focused on connections between chromatin remodeling enzymes, arginine methyltransferases and JumonjiC domain proteins that are or are predicted to be chromatin modifying enzymes.  Additional work has explores changes in higher-order gene organization that result from differentiation and signal transduction mechanisms that modify the activities of SWI/SNF chromatin remodeling enzymes via post-translational modifications of the individual enzyme subunits.