Authors:
ES Wong, BM Schmitt, A Kazachenka, D Thybert, A Redmond, F Connor, TF Rayner, C Feig, AC Ferguson-Smith, JC Marioni, DT Odom, P Flicek
Journal name: 
Nat Commun
Citation info: 
8(1):1092
Abstract: 
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.
DOI: 
http://doi.org/10.1038/s41467-017-01037-x
Research group: 
Odom Group, Marioni Group
E-pub date: 
23 Oct 2017