ArticleNature communications2023
An autoimmune pleiotropic SNP modulates IRF5 alternative promoter usage through ZBTB3-mediated chromatin looping.
Article in Nature communications, 2023. 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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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Genome-Wide CRISPR Screen Identifies a microRNA Orchestrating Pleiotropic Resistance to Targeted Therapy and T Cell Immunity in Melanoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Systematic transcriptome analysis reveals the function of alternative promoters in hematopoietic lineages.Stem cell reports · 2026Article
- Review
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- Multidimensional mapping of stimulation-responsive regulatory elements and candidate causal variants in T cell activation.Science advances · 2026Article
- Shared genetic architecture and potential comorbid mechanisms between rheumatoid arthritis and idiopathic pulmonary fibrosis.Clinical rheumatology · 2026Article
- Endogenous fine-mapping and prioritization of functional regulatory elements in complex genetic loci.Cell genomics · 2025Article
- Analysis of biased allelic enhancer activity of schizophrenia-linked common variants.Communications biology · 2025Article
- An Integrated Database for Exploring Alternative Promoters in Animals.Scientific data · 2025Article
- A compendium of genetic variations associated with promoter usage across 49 human tissues.Nature communications · 2024Article
- SMCHD1 activates the expression of genes required for the expansion of human myoblasts.Nucleic acids research · 2024Article
- Genetic polymorphisms in genes involved in the type I interferon system (STAT4 and IRF5): association with Asian SLE patients.Clinical rheumatology · 2024Review
- Polymerization of ZBTB transcription factors regulates chromatin occupancy.Molecular cell · 2024Article
- Identification and characterization of whole blood gene expression and splicing quantitative trait loci during early to mid-lactation of dairy cattle.BMC genomics · 2024Article
- Integrative high-throughput enhancer surveying and functional verification divulges a YY2-condensed regulatory axis conferring risk for osteoporosis.Cell genomics · 2024Article
- Breaking barriers: advancing cellular therapies in autoimmune disease management.Frontiers in immunology · 2024Review
- Landscape of enhancer disruption and functional screen in melanoma cells.Genome biology · 2023Article
- Inferring CTCF-binding patterns and anchored loops across human tissues and cell types.Patterns (New York, N.Y.) · 2023Article
- Allele-specific chromatin looping promotes IRF5-dependent autoimmunity.Nature reviews. Rheumatology · 2023Article
- 3D genome organization and epigenetic regulation in autoimmune diseases.Frontiers in immunology · 2023Review
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Authors and funding
23 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic sharing is extensively observed for autoimmune diseases, but the causal variants and their underlying molecular mechanisms remain largely unknown. Through systematic investigation of autoimmune disease pleiotropic loci, we found most of these shared genetic effects are transmitted from regulatory code. We used an evidence-based strategy to functionally prioritize causal pleiotropic variants and identify their target genes. A top-ranked pleiotropic variant, rs4728142, yielded many lines of evidence as being causal. Mechanistically, the rs4728142-containing region interacts with the IRF5 alternative promoter in an allele-specific manner and orchestrates its upstream enhancer to regulate IRF5 alternative promoter usage through chromatin looping. A putative structural regulator, ZBTB3, mediates the allele-specific loop to promote IRF5-short transcript expression at the rs4728142 risk allele, resulting in IRF5 overactivation and M1 macrophage polarization. Together, our findings establish a causal mechanism between the regulatory variant and fine-scale molecular phenotype underlying the dysfunction of pleiotropic genes in human autoimmunity.
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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.