Unravelling the logic of gene regulation by distal DNA elements

Unravelling the logic of gene regulation by distal DNA elements

Dr Mikhail Spivakov, Functional Gene Control, MRC London Institute of Medical Sciences

Host: Dr Patrick Varga-Weisz

 Abstract:
Three-dimensional chromatin organisation plays a major role in metazoan gene regulation. However, the dynamic nature of genomic architecture across cell types and its effect on lineage commitment are still not fully understood. We have used Promoter-Capture Hi-C to identify distal sequences interacting with the majority of annotated promoters in human cells globally and at high resolution. I will highlight two projects: (1) the analysis of interactome rewiring upon human ES cell commitment, with implications for gene regulation by multiple enhancers and (2) the profiling of promoter interactions in 17 primary haemopoietic cell types and using this information for linking common disease variants with putative target genes and pathways. Taken together, this work demonstrates the power of high-resolution interactome profiling for gaining insights into both global gene regulatory principles and for understanding the mechanisms of specific diseases.