Investigating principles of the regulatory chromatin context and incorporating them into computational models for gene regulation (360G-Wellcome-203728_Z_16_A)

The mammalian genome is hierarchically structured into domains that restrict and shape the accessible chromatin environment for every genomic element. This context has fundamental implications for transcriptional regulation, by defining which regulatory elements have access to a gene at any given time. Novel experimental techniques are being used to investigate this folding at high resolution. Current computational methods for analyzing these data and models for predicting properties of gene regulation are limited in capturing the emerging principles of DNA folding. We will investigate the principles of chromatin folding with large scale, high resolution chromatin Capture-C experiments, mapping the regulatory domains of mouse embryonic stem cells and differentiated erythroid cells. We will develop computational methods better suited to analyze these data and explore models for integrating the large scale, three dimensional chromatin context to prediction tasks. We expect this to have a significant impact on our ability to interpret the vast amount of sequence mutations and polymorphism in the regulatory genome.