Understanding how the NuRD complex functions in mouse embryonic stem cells (mESC's)

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Embryonic stem (ES) cells are pluripotent; they can either self-renew or differentiate into any of the body's specialised cell types. Pluripotency is maintained by a core set of transcription factors-proteins that bind to regulatory regions of genes and promote their expression. The Nucleosome Remodelling and Deacetylase (NuRD) complex plays a central role in controlling transcription factor binding to allow ES cells to differentiate. This project will use a form of super-resolution microscopy known as 3D single-molecule imaging to investigate how NuRD controls the binding of transcriptional regulators at their target genes. These regulators bind at enhancer regions, stretches of DNA near a gene that often need to be brought into proximity with the rest of a gene to enable transcription-but the mechanism is not fully understood. This project will therefore also aim to study how NuRD regulates the proximity of enhancers to their cognate genes and directly visualise the effect this has on the kinetics of transcription at those genes.