Oral Presentation Society for Molecular Biology and Evolution Conference 2016

Interplay of cis and trans mechanisms driving transcription factor binding, chromatin, and gene expression evolution (#195)

Emily S Wong 1 2 , Bianca Schmitt 3 , John Marioni 1 , Duncan Odom 3 , Paul Flicek 1
  1. European Bioinformatics Institute (EMBL-EBI), Cambridge, UK
  2. University of Queensland, St Lucia, QLD, Australia
  3. Cancer Resesarch UK, University of Cambridge, Cambridge, UK

Noncoding regulatory variants play a central role in the genetics of human diseases and in evolution. To elucidate the regulatory mechanisms underlying transcription factor (TF) binding variations in mammals, we measured allele-specific TF binding affinity of three liver-specific TFs between crosses of two inbred mouse strains. We classified over 45,000 binding events to one of four regulatory categories: conserved/non-differential-acting, cis, trans, both cis and trans. Our results highlight the dominance of additively-inherited cis-driven variation in TF occupancy variation. Trans-acting variations are most often dominantly inherited. Cis-acting variants lead to local coordination of TF occupancies that decays with distance and distal coordination which may be modulated by long-range chromatin contacts. Our results reveal the interlinking regulatory mechanisms that interplay to drive TF occupancy, chromatin state, and gene expression in complex mammalian cell states.