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

Emily S. Wong, Bianca M. Schmitt, Anastasiya Kazachenka, David Thybert, Aisling Redmond, Frances Connor, Tim F. Rayner, Christine Feig, Anne C. Ferguson-Smith, John C. Marioni, Duncan T. Odom () and Paul Flicek ()
Additional contact information
Emily S. Wong: Wellcome Genome Campus
Bianca M. Schmitt: University of Cambridge, Cancer Research UK—Cambridge Institute, Li Ka Shing Centre
Anastasiya Kazachenka: University of Cambridge
David Thybert: Wellcome Genome Campus
Aisling Redmond: University of Cambridge, Cancer Research UK—Cambridge Institute, Li Ka Shing Centre
Frances Connor: University of Cambridge, Cancer Research UK—Cambridge Institute, Li Ka Shing Centre
Tim F. Rayner: University of Cambridge, Cancer Research UK—Cambridge Institute, Li Ka Shing Centre
Christine Feig: University of Cambridge, Cancer Research UK—Cambridge Institute, Li Ka Shing Centre
Anne C. Ferguson-Smith: University of Cambridge
John C. Marioni: Wellcome Genome Campus
Duncan T. Odom: University of Cambridge, Cancer Research UK—Cambridge Institute, Li Ka Shing Centre
Paul Flicek: Wellcome Genome Campus

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-017-01037-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01037-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-01037-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().