Mechanisms of long-range enhancer function
Supervisor: Professor Wendy Bickmore
The complexity of human development, health and disease is dependent on the precise and responsive control of gene expression driven by regulatory elements – termed enhancers - embedded in the vast swathes of the non-coding human genome. We do not understand how enhancers work at locations in the genome distant from the genes they regulate, but the three-dimensional (3D) folding of the genome is thought to be important.
We investigate the fundamental mechanisms of enhancer function and the genomic context of enhancer function, by deploying and developing cutting-edge techniques in advanced imaging, synthetic biology, molecular and cell biology. Building on our discover that cohesin is required for enhancers to act over large genomic distances, this project aims to determine the precise distance limits for cohesin-dependent enhancer activation and the role of other components of the cohesin complex.
Kane L, Williamson I, Flyamer IM, Kumar Y, Hill RE, Lettice LA, Bickmore WA. (2022) Cohesin is required for long-range enhancer action at the Shh locus. Nat. Struct. Mol. Biol., 29:891-897.