RT Journal Article
SR Electronic
T1 Interplay of cis and trans mechanisms driving transcription factor binding, chromatin, and gene expression evolution
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 059873
DO 10.1101/059873
A1 Emily S Wong
A1 Bianca M Schmitt
A1 Anastasiya Kazachenka
A1 David Thybert
A1 Aisling Redmond
A1 Frances Connor
A1 Tim F Rayner
A1 Christine Feig
A1 Anne C. Ferguson-Smith
A1 John C Marioni
A1 Paul Flicek
A1 Duncan T Odom
YR 2016
UL http://biorxiv.org/content/early/2016/06/19/059873.abstract
AB Noncoding regulatory variants play a central role in the genetics of human diseases and in evolution. We measured allele-specific TF binding affinity of three liver-specific TFs between crosses of two inbred mouse strains to elucidate the regulatory mechanisms underlying transcription factor (TF) binding variations in mammals. Our results highlight the preeminence of cis-acting variants on TF occupancy divergence. TF 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 TF 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 TF occupancy, chromatin state, and gene expression in complex mammalian cell states.