ArticleNature communications2022
Lupus enhancer risk variant causes dysregulation of IRF8 through cooperative lncRNA and DNA methylation machinery.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- The rs713586 risk variant dysregulates ADCY3 rather than DNAJC27, leading to obesity through ZFP42-TET1-mediated DNA methylation.EBioMedicine · 2026Article
- The castration-resistant prostate cancer-associated SNP rs11067228 facilitates neuroendocrine differentiation through an enhancer-mediated chromatin interaction with SRRM4.International journal of biological sciences · 2026Article
- Mapping organ-associated autoantigenic landscapes in systemic lupus erythematosus.Frontiers in immunology · 2026Review
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- Ras-MAPK pathway in patients with lupus nephritis.Lupus science & medicine · 2025Article
- The Polygenic Nature of Multiple Sclerosis: Genetic Variants, Immunological Modulation, and Environmental Connections.Endocrine, metabolic & immune disorders drug targets · 2025Review
- New mechanism of LncRNA: In addition to act as a ceRNA.Non-coding RNA research · 2024Review
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- Systemic lupus erythematosus genetics: insights into pathogenesis and implications for therapy.Nature reviews. Rheumatology · 2024Review
- The roles of IRF8 in nonspecific orbital inflammation: an integrated analysis by bioinformatics and machine learning.Journal of ophthalmic inflammation and infection · 2024Article
- Type I Interferons in Systemic Autoimmune Rheumatic Diseases: Pathogenesis, Clinical Features and Treatment Options.Mediterranean journal of rheumatology · 2024Review
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- eRNAbase: a comprehensive database for decoding the regulatory eRNAs in human and mouse.Nucleic acids research · 2024Article
- Type I Interferons in Autoimmunity: Implications in Clinical Phenotypes and Treatment Response.The Journal of rheumatology · 2023Review
- TET (Ten-eleven translocation) family proteins: structure, biological functions and applications.Signal transduction and targeted therapy · 2023Review
- 3D genome organization and epigenetic regulation in autoimmune diseases.Frontiers in immunology · 2023Review
- Modeling of horizontal pleiotropy identifies possible causal gene expression in systemic lupus erythematosus.Frontiers in lupus · 2023Article
- WhichTF is functionally important in your open chromatin data?PLoS computational biology · 2022Article
- SLE risk variant regulates IRF8 expression.Nature reviews. Rheumatology · 2022Article
- Insights into the role of long non-coding RNAs in DNA methylation mediated transcriptional regulation.Frontiers in molecular biosciences · 2022Review
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Authors and funding
25 authors at 6 institutions in 3 countries.
Funding
Abstract
Despite strong evidence that human genetic variants affect the expression of many key transcription factors involved in autoimmune diseases, establishing biological links between non-coding risk variants and the gene targets they regulate remains a considerable challenge. Here, we combine genetic, epigenomic, and CRISPR activation approaches to screen for functional variants that regulate IRF8 expression. We demonstrate that the locus containing rs2280381 is a cell-type-specific enhancer for IRF8 that spatially interacts with the IRF8 promoter. Further, rs2280381 mediates IRF8 expression through enhancer RNA AC092723.1, which recruits TET1 to the IRF8 promoter regulating IRF8 expression by affecting methylation levels. The alleles of rs2280381 modulate PU.1 binding and chromatin state to regulate AC092723.1 and IRF8 expression differentially. Our work illustrates an integrative strategy to define functional genetic variants that regulate the expression of critical genes in autoimmune diseases and decipher the mechanisms underlying the dysregulation of IRF8 expression mediated by lupus risk variants.
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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.