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Subtle changes in chromatin loop contact propensity are associated with differential gene regulation and expression

Author

Listed:
  • William W. Greenwald

    (University of California, San Diego)

  • He Li

    (University of California, San Diego
    Human Genome Sequencing Center, Baylor College of Medicine)

  • Paola Benaglio

    (University of California, San Diego)

  • David Jakubosky

    (University of California, San Diego
    University of California, San Diego)

  • Hiroko Matsui

    (University of California, San Diego)

  • Anthony Schmitt

    (Arima Genomics)

  • Siddarth Selvaraj

    (Arima Genomics)

  • Matteo D’Antonio

    (University of California, San Diego
    University of California, San Diego)

  • Agnieszka D’Antonio-Chronowska

    (University of California, San Diego)

  • Erin N. Smith

    (University of California, San Diego)

  • Kelly A. Frazer

    (University of California, San Diego
    University of California, San Diego)

Abstract

While genetic variation at chromatin loops is relevant for human disease, the relationships between contact propensity (the probability that loci at loops physically interact), genetics, and gene regulation are unclear. We quantitatively interrogate these relationships by comparing Hi-C and molecular phenotype data across cell types and haplotypes. While chromatin loops consistently form across different cell types, they have subtle quantitative differences in contact frequency that are associated with larger changes in gene expression and H3K27ac. For the vast majority of loci with quantitative differences in contact frequency across haplotypes, the changes in magnitude are smaller than those across cell types; however, the proportional relationships between contact propensity, gene expression, and H3K27ac are consistent. These findings suggest that subtle changes in contact propensity have a biologically meaningful role in gene regulation and could be a mechanism by which regulatory genetic variants in loop anchors mediate effects on expression.

Suggested Citation

  • William W. Greenwald & He Li & Paola Benaglio & David Jakubosky & Hiroko Matsui & Anthony Schmitt & Siddarth Selvaraj & Matteo D’Antonio & Agnieszka D’Antonio-Chronowska & Erin N. Smith & Kelly A. Fra, 2019. "Subtle changes in chromatin loop contact propensity are associated with differential gene regulation and expression," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08940-5
    DOI: 10.1038/s41467-019-08940-5
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    Cited by:

    1. Kaela M. Varberg & Esteban M. Dominguez & Boryana Koseva & Joseph M. Varberg & Ross P. McNally & Ayelen Moreno-Irusta & Emily R. Wesley & Khursheed Iqbal & Warren A. Cheung & Carl Schwendinger-Schreck, 2023. "Extravillous trophoblast cell lineage development is associated with active remodeling of the chromatin landscape," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    2. Phoebe Lut Fei Tam & Ming Fung Cheung & Lu Yan Chan & Danny Leung, 2024. "Cell-type differential targeting of SETDB1 prevents aberrant CTCF binding, chromatin looping, and cis-regulatory interactions," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Yi Liao & Juntao Wang & Zhangsheng Zhu & Yuanlong Liu & Jinfeng Chen & Yongfeng Zhou & Feng Liu & Jianjun Lei & Brandon S. Gaut & Bihao Cao & J. J. Emerson & Changming Chen, 2022. "The 3D architecture of the pepper genome and its relationship to function and evolution," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    4. Matteo D’Antonio & Jennifer P. Nguyen & Timothy D. Arthur & Hiroko Matsui & Agnieszka D’Antonio-Chronowska & Kelly A. Frazer, 2023. "Fine mapping spatiotemporal mechanisms of genetic variants underlying cardiac traits and disease," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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