Uncoupling evolutionary changes in DNA sequence, transcription factor occupancy and enhancer activity.

ABSTRACT: Sequence variation within enhancers plays a major role in both evolution and disease, yet its functional impact on transcription factor (TF) occupancy and enhancer activity remains poorly understood. Here, we assayed the binding of five essential TFs over multiple stages of embryogenesis in two distant Drosophila species (with 1.4 substitutions per neutral site), identifying thousands of orthologous enhancers with conserved or diverged combinatorial occupancy. We used these binding signatures to dissect two properties of developmental enhancers: (1) potential TF cooperativity, using signatures of co-associations and co-divergence in TF occupancy. This revealed conserved combinatorial binding despite sequence divergence, suggesting protein-protein interactions sustain conserved colle

SUBMITTER: Khoueiry P 

PROVIDER: S-EPMC5550276 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature