Elucidating how the Sotos Syndrome gene NSD1 controls gene expression during neuronal differentiation.

Each cell has the same genetic information, our DNA. Yet, our body consists of many different cell types (eg. muscle cells, brain cells, etc). To become a specific cell type, our cells have the ability to turn genes in our DNA on or off. This selective control of genes is achieved via “epigenetics”, which means on top (epi-) of our genes (genetics). Epigenetics involves chemical changes to proteins that organize our DNA, which are called histones. Changes to histones are made by epigenetic enzymes. When epigenetic enzymes are defective the wrong changes are made to histones. In turn, the wrong genes are turned on or off, leading to disease. An example of such a disease is Sotos Syndrome, a neurodevelopmental disorder caused by a defect in the epigenetic enzyme NSD1. Exactly how defective NSD1 leads to misguided control of genes is unknown. To examine this, I will use gene editing and delete NSD1 in neuronal precursor cells. Next, I will study the effect of defective NSD1 on histone changes and identify which genes are wrongfully turned on or off in these cells. The results from this study will show how defective NSD1 leads to misguided gene control and can help identify new options for the treatment of Sotos Syndrome.