Mouse B2 SINE elements function as IFN-inducible enhancers
- University of Colorado Boulder, United States
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.
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Mouse SINE B2 elements function as IFN-inducible enhancer elementsNCBI Gene Expression Omnibus, GSE202574.
Article and author information
Author details
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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Mouse B2 SINE elements function as IFN-inducible enhancers
eLife 12:e82617.
https://doi.org/10.7554/eLife.82617
