Regulators of Epidermal Gene Expression 

Epidermal tissue homeostasis requires the precise balance between progenitor self-renewal and tissue differentiation. Disruption of this balance underlies a number of human diseases including chronic wound healing, psoriasis and cancer. This R00 proposal aims to characterize essential epidermal regulators that maintain epidermal tissue homeostasis. First, my group will focus on understanding the roles of chromatin remodeling complexes such as the BAF/SWI/SNF complex in human epidermal tissue. The BAF complex, composed of 11 subunits encoded by 20 genes, is frequently mutated in human diseases such as cancer and psoriasis. My preliminary characterization of the BAF complex indicates that it is essential for both epidermal progenitor maintenance and for activating terminal tissue differentiation. The goal of the first aim is to dissect the gene regulatory mechanism controlled by specific BAF subunits in normal epidermal tissue homeostasis. Second, my group will characterize the roles of protein arginine methylation in human epidermal tissue. Protein arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), modulates the interactions with other proteins and nucleic acids. The PRMTs are frequently overexpressed/mutated in epithelial cancer, and many of them are required for early embryonic development. In human epidermal tissue, I have identified an essential role of PRMT1 in epidermal progenitor maintenance, and have further identified 37 unique PRMT1-interacting proteins. How PRMT1 cooperates with its interacting proteins to control progenitor gene expression remains incompletely understood. The second aim of this research plan is directed at elucidating the gene regulatory mechanism controlled by PRMT1 and its interacting partners. The long-term goal of my research is to uncover novel gene regulatory mechanisms in human epidermal tissue homeostasis, and to provide new insights for human disease therapies.