Determining the mechanisms regulating chromatin architecture in cell fate decisions.

During development, it is important to have the correct cell type in the correct place at the correct time. This is controlled by biological signals, that are interpreted by regions of non-coding DNA called regulatory elements, modulating gene expression. It is not clear how regulatory elements function to control gene expression. I will use a mouse embryonic stem-cell model of motor-neuron specification to study the control of Olig2, by two regulatory units. These regulatory units work in different combinations in motor-neurons in the hindbrain and spinal-cord. I will identify interactions between Olig2 and its regulatory units and use gene editing to alter where and when these interactions occur, assessing the effect on Olig2 expression during motor neuron formation. I will also force interactions to identify how regulatory elements control motor neuron-specification. This project will give new understanding of regulatory element function in development and disease in the brain and spinal-cord.