The role of mammalian enhancers in gene regulation and its evolution

All cells in an organism share the same genome sequence. By expressing different genes in different contexts, multicellular organisms achieve cellular complexity – adult humans have a few hundred different cell types that all derived from one fertilized egg cell through differential regulation of developmental genes. Enhancers, distal cis-regulatory elements, play an important role in facilitating cell type- and time point-specific gene regulation. Typically, one gene is regulated by many enhancers, each of which is active in a limited spatiotemporal context. In contrast to mutations in the promoter or the coding sequence, the effect of evolutionary change occurring at an enhancer can be restricted to the context in which the enhancer is active. Studying enhancer evolution is therefore instructional to understand the origin of mammalian complexity and lineage-specific adaptations.

Research in our lab employs computational and functional genomics to interrogate enhancer evolution in mammals. Using computational approaches we identify enhancers and uncover patterns indicative of evolutionary change. We further use genome-scale assays to identify enhancers and to explore their activity in cell model systems derived from induced pluripotent stem cells (iPSCs) from different mammalian species. Please see Publications for recent research output from our lab.