ArticleMolecular and cellular biology2015
Long-Range Transcriptional Control of the Il2 Gene by an Intergenic Enhancer.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 23 citations in OpenAlex.
- The Role ofInternational journal of molecular sciences · 2026Article
- ZFP612 controls neuropathic pain through epigenetic repression of Il1rl1 within the silencer-promoter loop in primary sensory neurons of male mice.Nature communications · 2025Article
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- Evolution of γ chain cytokines: Mechanisms, methods and applications.Computational and structural biotechnology journal · 2022Review
- SOX-5 activates a novel RORγt enhancer to facilitate experimental autoimmune encephalomyelitis by promoting Th17 cell differentiation.Nature communications · 2021Article
- Immune Regulation in Time and Space: The Role of Local- and Long-Range Genomic Interactions in Regulating Immune Responses.Frontiers in immunology · 2021Review
- Molecular Mechanism of Mesenchyme Homeobox 1 in Transforming Growth Factor β1-InducedFrontiers in molecular biosciences · 2020Article
- Early Notch Signals Induce a Pathogenic Molecular Signature during Priming of Alloantigen-Specific Conventional CD4Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- The γF1000Research · 2017Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Interleukin-2 (IL-2) is a potent cytokine with roles in both immunity and tolerance. Genetic studies in humans and mice demonstrate a role for Il2 in autoimmune disease susceptibility, and for decades the proximal Il2 upstream regulatory region has served as a paradigm of tissue-specific, inducible gene regulation. In this study, we have identified a novel long-range enhancer of the Il2 gene located 83 kb upstream of the transcription start site. This element can potently enhance Il2 transcription in recombinant reporter assays in vitro, and the native region undergoes chromatin remodeling, transcribes a bidirectional enhancer RNA, and loops to physically interact with the Il2 gene in vivo in a CD28-dependent manner in CD4(+) T cells. This cis regulatory element is evolutionarily conserved and is situated near a human single-nucleotide polymorphism (SNP) associated with multiple autoimmune disorders. These results indicate that the regulatory architecture of the Il2 locus is more complex than previously appreciated and suggest a novel molecular basis for the genetic association of Il2 polymorphism with autoimmune disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.