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

Author

Listed:
  • 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
    University of Cambridge, Cancer Research UK—Cambridge Institute, Li Ka Shing Centre)

  • Duncan T. Odom

    (University of Cambridge, Cancer Research UK—Cambridge Institute, Li Ka Shing Centre
    Wellcome Trust Sanger Institute, Wellcome Genome Campus)

  • Paul Flicek

    (Wellcome Genome Campus
    Wellcome Trust Sanger Institute, Wellcome Genome Campus)

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.

Suggested Citation

  • 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. Odo, 2017. "Interplay of cis and trans mechanisms driving transcription factor binding and gene expression evolution," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01037-x
    DOI: 10.1038/s41467-017-01037-x
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    Cited by:

    1. Jiankai Wei & Wei Zhang & An Jiang & Hongzhe Peng & Quanyong Zhang & Yuting Li & Jianqing Bi & Linting Wang & Penghui Liu & Jing Wang & Yonghang Ge & Liya Zhang & Haiyan Yu & Lei Li & Shi Wang & Liang, 2024. "Temporospatial hierarchy and allele-specific expression of zygotic genome activation revealed by distant interspecific urochordate hybrids," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. Kaitlyn A. Lagattuta & Hannah L. Park & Laurie Rumker & Kazuyoshi Ishigaki & Aparna Nathan & Soumya Raychaudhuri, 2024. "The genetic basis of autoimmunity seen through the lens of T cell functional traits," Nature Communications, Nature, vol. 15(1), pages 1-6, December.
    3. Sarah E. Harris & Maria S. Alexis & Gilbert Giri & Francisco F. Cavazos & Yue Hu & Jernej Murn & Maria M. Aleman & Christopher B. Burge & Daniel Dominguez, 2024. "Understanding species-specific and conserved RNA-protein interactions in vivo and in vitro," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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