Cis-regulatory co-option of a transposon family reinforces cell identity across the immune system
Year: 2026
Type: article
Abstract: Transposable elements (TEs) comprise about half of the human and mouse genomes and contribute to gene regulation during immune responses. However, how TEs acquire cis-regulatory functions during immune cell development remains poorly understood. Here, we analyzed hundreds of datasets profiling chromatin accessibility, gene expression, transcription factor occupancy and DNA-DNA contact across diverse mouse and human immune cell types. We identified two rodent-specific TE subfamilies, ORR1E and ORR1D2 (collectively, ODE) that have diversified after genomic insertion into cell type-specific enhancers across the mouse immune system. Post-insertion mutations in ODE loci generated differential binding sites for lineage-specifying transcription factors. ODEs showed evidence of evolutionary sequence constraint and contacted promoters of hundreds of genes in immune cells. Predicted ODE target genes were enriched for cell type-specific functions and showed increased expression in mouse compared to human cell types lacking ODEs. Together, these findings show how a single TE family can diversify after genomic spread to generate cell type-specific enhancers that reinforce lineage-specific gene programs.
Source: The EMBO Journal
Institution: Cornell University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $7,990
Awards: The developmental layers in the CD8+ T cell response to chronic infection, A Single Comprehensive Assay for Gene Regulatory Profiling Optimized for Minimal Sample Input Requirements, Genomic and Physiological Impact of Transposable Elements., Impact of transposable elements on cis-regulatory variation in T cell activation, Regulatory Crosstalk Between Human Endogenous Retroviruses, HIV, and EBV, in Lymphoma
OpenAlex ID: W7117246223