Distinguished Lecture - The Remote Control of Gene Expression
It is now appreciated that long-range enhancers - found as far away as 1 megabase from their target gene and located either in intergenic regions or in introns - are key in controlling the precise spatial and temporal expression of genes. In contrast to the 20,000 or so genes in our genome, there may be hundreds of thousands, or even millions, of enhancers. Deletion, translocation or point mutations can abrogate the function of these elements in Mendelian diseases associated with severe phenotypes. However, the majority of human genetic variation associated with common and complex disease and quantitative traits also maps to intergenic regions that are likely the site of enhancers. Therefore, lessons learnt from studying enhancer dysfunction in rare disease will be important for an understanding of milder phenotypes.
It is hard to envisage how distant enhancers function if one only considers the genome as a linear DNA sequence. Rather, three-dimensional chromatin folding in the nucleus must play a fundamental role in enhancer-promoter communication. I will describe our work using different experimental approaches to investigate and manipulate the three-dimensional folding of the mammalian genome at genetically defined long-range regulatory elements. Different models of enhancer function will be discussed.
The Babraham Distinguished Lecture Series
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