Enhancer DNA methylation dynamics during early mammalian development
Enhancers are regulatory elements (specific DNA-sequences) that can drive the expression of protein-coding genes, even when located a great distance away from them. They interact with their target genes via 3D loops that form in the DNA molecule. DNA methylation is an important epigenetic mark (a chemical modification of DNA) that can inhibit gene expression when located nearby (at the promoter), but it is not known how DNA methylation affects enhancers.
My aim is to understand the effect of DNA methylation on enhancer activity. I will use a novel screen-based approach and cutting-edge genomics approaches to interrogate this question in cell-based models of early development (embryonic stem cells), where DNA methylation levels can be controlled dynamically.
My findings will improve our basic understanding of gene regulation and indicate how we might modulate enhancer activity in disease contexts.