Abstract

Regulatory networks underlying innate immunity continually face selective pressures to adapt to new and evolving pathogens. Transposable elements (TEs) can affect immune gene expression as a source of inducible regulatory elements, but the significance of these elements in facilitating evolutionary diversification of innate immunity remains largely unexplored. Here, we investigated the mouse epigenomic response to type II interferon (IFN) signaling and discovered that elements from a subfamily of B2 SINE (B2_Mm2) contain STAT1 binding sites and function as IFN-inducible enhancers. CRISPR deletion experiments in mouse cells demonstrated that a B2_Mm2 element has been co-opted as an enhancer driving IFN-inducible expression of Dicer1. The rodent-specific B2 SINE family is highly abundant in the mouse genome and elements have been previously characterized to exhibit promoter, insulator, and non-coding RNA activity. Our work establishes a new role for B2 elements as inducible enhancer elements that influence mouse immunity, and exemplifies how lineage-specific TEs can facilitate evolutionary turnover and divergence of innate immune regulatory networks.

Data availability

Raw and processed sequencing data generated in this study have been submitted to the NCBI Gene Expression Omnibus (GEO) with accession number GSE202574.

The following data sets were generated

Article and author information

Author details

  1. Isabella Horton

    Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Conor J Kelly

    Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2410-7892
  3. Adam Dziulko

    Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. David M Simpson

    Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Edward B Chuong

    Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, United States
    For correspondence
    edward.chuong@colorado.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5392-937X

Funding

National Institutes of Health (1R35GM128822)

  • Edward B Chuong

David and Lucile Packard Foundation

  • Edward B Chuong

Boettcher Foundation

  • Isabella Horton
  • Edward B Chuong

Alfred P. Sloan Foundation

  • Edward B Chuong

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2023, Horton et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Isabella Horton
  2. Conor J Kelly
  3. Adam Dziulko
  4. David M Simpson
  5. Edward B Chuong
(2023)
Mouse B2 SINE elements function as IFN-inducible enhancers
eLife 12:e82617.
https://doi.org/10.7554/eLife.82617

Share this article

https://doi.org/10.7554/eLife.82617

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