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

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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Author Wong, Emily S.
Last Updated November 20, 2019, 16:44 (UTC)
Created August 1, 2019, 10:30 (UTC)
Article Host Type publisher
Article Is Open Access true
Article License Type cc-by
Article Version Type publishedVersion
Citation Report https://scite.ai/reports/10.1038/s41467-017-01037-x
DOI 10.1038/s41467-017-01037-x
Date Last Updated 2019-08-01T10:29:35.889914
Evidence oa journal (via doaj)
Funder code(s)
Journal Is Open Access true
Open Access Status gold
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Publisher URL https://doi.org/10.1038/s41467-017-01037-x