Master of Science
Dr. Shawn Li
In an effort to expand the histone code, we examine a novel site of methylation on lysine 43 of histone H2B. In mouse embryonic stem cells (ESCs), KDM5b acts as the lysine demethylase for H2BK43me2, diminishing this histone mark as cells differentiate. We utilize a synthetic peptide mimetic corresponding to amino acids 37-49 of histone H2B in order to sterically inactivate KDM5b enzyme. The addition of inhibitor peptide into culture enhanced stem cell differentiation, upregulating cell cycle and neural-specific markers while downregulating the expression of pluripotency genes. Global gene analysis patterns of peptide-treated ESCs were representative of differentiated cell populations. Applying a novel inhibition method, we reveal an accelerated rate of stem cell differentiation through the upregulation of KDM5b targets. Our investigation serves to elucidate the role of histone H2BK43 methylation in an epigenetically regulated model of development.
Zhu, Wendy, "Investigation of histone lysine methylation in stem cell differentiation using inhibitor peptide" (2012). University of Western Ontario - Electronic Thesis and Dissertation Repository. Paper 496.