Evolution's Rapid Rewiring of Mammalian Genome Regulation

Mammals are characterised by a wide range of morphological diversity arising from a largely consistent set of genes. A significant fraction of these differences are assumed to derive from differences in transcriptional regulation. We have created maps of transcription factor binding, chromatin organising proteins and active enhancers and promoters across a large number of mammalian species in an attempt to understand these changes at a molecular level. These data provide insight into the evolutionary origin and persistence of regulatory sequences as well as characterise the vast majority of regulatory regions that are not shared in the common ancestor of all mammals. By investing both major mammalian orders and closely related rodent species, we can understand the greater context for the first steps of evolutionary change between species. We have also estimated the contribution of individual transcription factor binding events to tissue-specific regulation and determined the mode of inheritance for these binding sites.