Grant: Project Grant

Each cell in an individual has the same genetic code, our DNA. Yet, our body consists of many different cell types. This is due the ability of our cells to turn genes on and off, depending on which genes are needed within that specific cell type. DNA in our cells is wrapped around protein scaffolds called histones. Chemical modifications to such histones act like levers that a cell uses to control whether to turn a gene on or off. We call the study of these modifications Epigenetics. Epigenetic enzymes modify specific amino acids on histones. These modifications can enable or disrupt the activity of other epigenetic enzymes, resulting in specific modifications at specific locations along the DNA. The balance between different histone modifications is disturbed when a specific epigenetic enzyme is defective, ie mutated, as observed in neurodevelopmental disorders and cancers with mutations in the genews encoding these proteins. When histones are modified at abnormal locations along the DNA it leads to malfunctioning gene control. It is unclear how disrupting the balance between histone modifications leads to misguided control of genes. To gain insight into this, we will first use gene editing to delete specific epigenetic enzymes. Then, we will examine the effect of such deletion on histone modifications and gene control. This allows us to show how disrupting the balance between histone modifications results in abnormal gene control and will shed light on how defective epigenetic enzymes can contribute to disease. These discoveries will assist in the development of new treatments for the neurodevelopmental disorders and cancers in which these epigenetic enzymes are mutated.