Kaiso overexpression promotes an interferon immune response in murine intestines
4 affiliations
- 1Department of Biology, McMaster University
- 2School of Interdisciplinary Science, McMaster University
- 3Department of Surgery, School of Medicine, Washington University
- 4Centre for Discovery in Cancer Research, McMaster University
Abstract
The POZ-ZF transcription factor Kaiso plays important roles in vertebrate development and tumorigenesis and binds DNA with dual-specificity at both a consensus DNA sequence and methyl-CpG sites. In murine intestines, Kaiso overexpression induces a chronic inflammatory phenotype that involves NFκB signaling and neutrophil activation. However, a thorough understanding of the molecular mechanisms and signaling pathways involved in the Kaiso-induced inflammatory response warrant further investigation. In this study, global transcriptomes of ileal tissue from 6-week-old Kaiso overexpressing transgenic (Kaiso Tg ) and non-transgenic (NonTg) control mice were generated by RNA sequencing and compared for differential gene expression prior to histologic inflammation. Functional analysis of differentially expressed genes identified an enrichment of genes involved in type I interferon immune response despite preserved epithelial architecture and the absence of neutrophil infiltration. Irf7, Isg15, Usp18 and Ifi44 were identified as key genes mediating type I interferon signaling in intestinal epithelial cells. We determined that Kaiso binds to and regulates the IRF7 promoter via the consensus Kaiso binding site (KBS). Additionally, promoter-reporter assays confirmed that Kaiso activated the minimal IRF7 promoter-reporter in a KBS-specific and methyl-CpG-independent manner. Collectively, our findings demonstrate that Kaiso overexpression activates a type I interferon gene program that precedes histologic inflammation and implicates IRF7 as a putative Kaiso target gene that mediates this response.
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BibTeX
@article{lessey2026kaiso,
title = {{Kaiso overexpression promotes an interferon immune response in murine intestines}},
author = {Lindyann R. Lessey and Hanad Adan and Shaiya C. Robinson and Roopali Chaudhary and Shruthilayaa Sivakumar and Stephanie Ali Fairbairn and Danial Mohammadi and Kyle Kim and Dereck Alleyne and Kathleen E. Houlahan and Pierre-André Bédard and Robert W. Cowan and Juliet M. Daniel},
journal = {BMC Genomics},
year = {2026},
month = jul,
doi = {10.1186/s12864-026-13047-5},
url = {https://doi.org/10.1186/s12864-026-13047-5},
note = {CC BY},
}
RIS
TY - JOUR
TI - Kaiso overexpression promotes an interferon immune response in murine intestines
AU - Lindyann R. Lessey
AU - Hanad Adan
AU - Shaiya C. Robinson
AU - Roopali Chaudhary
AU - Shruthilayaa Sivakumar
AU - Stephanie Ali Fairbairn
AU - Danial Mohammadi
AU - Kyle Kim
AU - Dereck Alleyne
AU - Kathleen E. Houlahan
AU - Pierre-André Bédard
AU - Robert W. Cowan
AU - Juliet M. Daniel
PY - 2026
DA - 2026/07/01
JO - BMC Genomics
DO - 10.1186/s12864-026-13047-5
UR - https://doi.org/10.1186/s12864-026-13047-5
AB - The POZ-ZF transcription factor Kaiso plays important roles in vertebrate development and tumorigenesis and binds DNA with dual-specificity at both a consensus DNA sequence and methyl-CpG sites. In murine intestines, Kaiso overexpression induces a chronic inflammatory phenotype that involves NFκB signaling and neutrophil activation. However, a thorough understanding of the molecular mechanisms and signaling pathways involved in the Kaiso-induced inflammatory response warrant further investigation. In this study, global transcriptomes of ileal tissue from 6-week-old Kaiso overexpressing transgenic (Kaiso Tg ) and non-transgenic (NonTg) control mice were generated by RNA sequencing and compared for differential gene expression prior to histologic inflammation. Functional analysis of differentially expressed genes identified an enrichment of genes involved in type I interferon immune response despite preserved epithelial architecture and the absence of neutrophil infiltration. Irf7, Isg15, Usp18 and Ifi44 were identified as key genes mediating type I interferon signaling in intestinal epithelial cells. We determined that Kaiso binds to and regulates the IRF7 promoter via the consensus Kaiso binding site (KBS). Additionally, promoter-reporter assays confirmed that Kaiso activated the minimal IRF7 promoter-reporter in a KBS-specific and methyl-CpG-independent manner. Collectively, our findings demonstrate that Kaiso overexpression activates a type I interferon gene program that precedes histologic inflammation and implicates IRF7 as a putative Kaiso target gene that mediates this response.
SN - 1471-2164
ER -