ArticleGenome biology2022
Epigenomic analysis reveals a dynamic and context-specific macrophage enhancer landscape associated with innate immune activation and tolerance.
Article in Genome biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Human Alu loci gain enhancer-type epigenetic modifications in monocytes during response to bacterial LPS.Epigenetics & chromatin · 2026Article
- Quantitative Control of Transposable Elements: From Genome Plasticity to Immune Regulatory Circuits.Cell biochemistry and function · 2026Review
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- The case for exploring innate memory in Plasmodium infection.Current opinion in microbiology · 2026Review
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- Context-specific regulatory genetic variation in MTOR dampens neutrophil-T cell crosstalk in pneumonia-associated sepsis.Nature communications · 2026Article
- Distinct transcriptional and epigenomic programs define Hofbauer cells in term placenta.JCI insight · 2026Article
- Macrophages: sentinels, warriors, and healers.Human molecular genetics · 2025Review
- Exploring the Causal Relationship Between Inflammatory Bowel Disease and Bell's Palsy Based on Inflammatory Proteins: A Mendelian Randomization Study.Brain and behavior · 2025Article
- Macrophage Reprogramming: Emerging Molecular Therapeutic Strategies for Nephrolithiasis.Biomolecules · 2025Review
- Nucleosome placement and polymer mechanics explain genomic contacts on 100 kb scales.Nucleic acids research · 2025Article
- SPI1 upregulated LILRB2 to enhance the immunosuppressive phenotype of LPS-tolerant macrophages by inhibiting TLR8-mediated MyD88/NF-κB signaling.Biology direct · 2025Article
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- Single-cell analysis reveals transcriptomic features and therapeutic targets in primary pulmonary lymphoepithelioma-like carcinoma.Communications biology · 2025Article
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- Optimizing approaches for targeted integration of transgenic cassettes by integrase-mediated cassette exchange in mouse and human stem cells.Stem cells (Dayton, Ohio) · 2025Article
- Robust estimation of cancer and immune cell-type proportions from bulk tumor ATAC-Seq data.eLife · 2024Article
- Epigenetic regulation of tumor immunity.The Journal of clinical investigation · 2024Review
- eRNAbase: a comprehensive database for decoding the regulatory eRNAs in human and mouse.Nucleic acids research · 2024Article
- Mapping the epigenomic landscape of human monocytes following innate immune activation reveals context-specific mechanisms driving endotoxin tolerance.BMC genomics · 2023Article
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Authors and funding
12 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundChromatin states and enhancers associate gene expression, cell identity and disease. Here, we systematically delineate the acute innate immune response to endotoxin in terms of human macrophage enhancer activity and contrast with endotoxin tolerance, profiling the coding and non-coding transcriptome, chromatin accessibility and epigenetic modifications.
resultsWe describe the spectrum of enhancers under acute and tolerance conditions and the regulatory networks between these enhancers and biological processes including gene expression, splicing regulation, transcription factor binding and enhancer RNA signatures. We demonstrate that the vast majority of differentially regulated enhancers on acute stimulation are subject to tolerance and that expression quantitative trait loci, disease-risk variants and eRNAs are enriched in these regulatory regions and related to context-specific gene expression. We find enrichment for context-specific eQTL involving endotoxin response and specific infections and delineate specific differential regions informative for GWAS variants in inflammatory bowel disease and multiple sclerosis, together with a context-specific enhancer involving a bacterial infection eQTL for KLF4. We show enrichment in differential enhancers for tolerance involving transcription factors NFκB-p65, STATs and IRFs and prioritize putative causal genes directly linking genetic variants and disease risk enhancers. We further delineate similarities and differences in epigenetic landscape between stem cell-derived macrophages and primary cells and characterize the context-specific enhancer activities for key innate immune response genes KLF4, SLAMF1 and IL2RA.
conclusionsOur study demonstrates the importance of context-specific macrophage enhancers in gene regulation and utility for interpreting disease associations, providing a roadmap to link genetic variants with molecular and cellular functions.
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