Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using polymer models

Our chromosomes are made up from a material called chromatin, which is essentially DNA packaged up with proteins. Different genes within our chromosomes need to be transcribed in different cell types, and at different stages of development; one way in which gene activation is regulated is through changing the three dimensional arrangement of the chromosome. Often transcription is activated by proteins binding at gene promoters and at other sites on the DNA called enhancers: in order for the gene to become active the chromatin has to fold in such a way as to bring the promoter into contact with the enhancer. I will present polymer simulations which allow us to predict how the binding of proteins (specifically the pattern of protein binding sites along the chromosome) drives the 3D arrangement of the chromosome, and how that regulates transcription. This has implications for understanding many genetic disorders in which the protein coding regions of genes are intact, but mutations within regulatory elements (such as promoters and enhancers) lead to mis-regulation.