Ancestral and derived transcriptional enhancers share regulatory sequence and a pleiotropic site affecting chromatin accessibility

Significance Form diversity is fueled by changes in the expression of genes that build organisms. New expression often results from the emergence of new DNA switches, known as transcriptional enhancers. Many enhancers are thought to appear through the recycling of older enhancers, a process called evolutionary co-option. Enhancer co-option is difficult to assess, and the molecular mechanisms explaining its prevalence are elusive. Using state-of-the-art quantification and analyses, we reveal that the sequences of an ancestral and a derived enhancer overlap extensively. They contain specific binding sites for regulators imparting spatial activities. We found that the two enhancers also share a site facilitating access to chromatin in a region where they overlap.