Presenter: Connor Littlefield, College of Life sciences, Nutrition, dietetics and food science
Authors: Connor Littlefield, Jeffrey S. Tessem
Faculty Advisor: Jeffery Tessem, College of Life Sciences, NDFS
Institution: Brigham Young University
Type 1 and type 2 diabetes are a result of beta cell death, and the body’s inability to replenish the beta cell pool. Fortunately, beta cell replication has been achieved in mice through overexpression of a key beta cell transcription factor, Nkx6.1. However, Nkx6.1 induced replication is effective only in young mice, and not in the aged. This is due to its inability to upregulate Nr4a1 and VGF, beta cell genes involved in proliferation. We suspected this was a result of an altered binding interaction between Nkx6.1 and another beta cell protein necessary for gene regulation. To identify proteins that interact with Nkx6.1, we used BioID analysis to tag all Nkx6.1 interacting proteins with biotin. Subsequent Mass Spectrometry analysis identified a list of candidate proteins that were then grouped by function through DAVID analysis. Results showed that Nkx6.1 binds to 5 key beta cell transcription factors Nr2c2, Lin54, Sirt7, Mef2d and Pdx1. Pdx1 was decided the most likely candidate as a co-regulator of beta cell function because of its important role in beta cell development and replication. Discovery of the interaction between these two key beta cell transcription factors provides insight into the mechanisms of beta cell replication that can be applied to diabetic patients and restore beta cell mass.