TY - JOUR T1 - Interplay of cis and trans mechanisms driving transcription factor binding and gene expression evolution JF - bioRxiv DO - 10.1101/059873 SP - 059873 AU - Emily S Wong AU - Bianca M Schmitt AU - Anastasiya Kazachenka AU - David Thybert AU - Aisling Redmond AU - Frances Connor AU - Tim F. Rayner AU - Christine Feig AU - Anne C. Ferguson-Smith AU - John C Marioni AU - Duncan T Odom AU - Paul Flicek Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/07/29/059873.abstract N2 - Noncoding regulatory variants play a central role in the genetics of human diseases and in evolution. Here we measure allele-specific transcription factor binding occupancy of three liver-specific transcription factors between crosses of two inbred mouse strains to elucidate the regulatory mechanisms underlying transcription factor binding variations in mammals. Our results highlight the pre-eminence of cis-acting variants on transcription factor occupancy divergence. Transcription factor binding differences linked to cis-acting variants generally exhibit additive inheritance, while those linked to trans-acting variants are most often dominantly inherited. Cis-acting variants lead to local coordination of transcription factor occupancies that decay with distance; distal coordination is also observed and may be modulated by long-range chromatin contacts. Our results reveal the regulatory mechanisms that interplay to drive transcription factor occupancy, chromatin state, and gene expression in complex mammalian cell states. ER -