Jun 19, 2016

Interplay of cis and trans mechanisms driving transcription factor binding and gene expression evolution

BioRxiv : the Preprint Server for Biology
Emily S WongPaul Flicek

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.

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Mentioned in this Paper

Transcription, Genetic
Gene Expression
Genetic Inheritance
Mammalian Cell
Transcription Factor Binding
Binding (Molecular Function)
Gene Regulatory Networks
Chromatin Location
Distal
Alleles

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