ArticleGenes & development2015
A dual cis-regulatory code links IRF8 to constitutive and inducible gene expression in macrophages.
Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 128 citations in OpenAlex.
- Multi-level transcriptional control of specific macrophage responses.The EMBO journal · 2026Review
- Regulation of Inducible Nitric Oxide Synthase (NOS2) Expression in Healthy and Inflamed Bowel: A Narrative Review.International journal of molecular sciences · 2026Review
- RANKL inhibits macrophage proinflammatory Toll-like receptor 2 and 4 signaling and impairs killing of intracellular bacteria.ImmunoHorizons · 2026Article
- Epromoters bind key stress-related transcription factors to regulate clusters of stress response genes.The EMBO journal · 2026Article
- PervasivebioRxiv : the preprint server for biology · 2025Article
- Microglia across evolution: from conserved origins to functional divergence.Cellular & molecular immunology · 2025Review
- Interplay Between KLF4, STAT, IRF, and NF-κB in VSMC and Macrophage Plasticity During Vascular Inflammation and Atherosclerosis.International journal of molecular sciences · 2025Review
- 3D4 cells exhibit transcriptional features inconsistent with alveolar macrophage identity.Veterinary research · 2025Article
- Review
- Integrative single-cell RNA-seq and ATAC-seq identifies transcriptional and epigenetic blueprint guiding osteoclastogenic trajectory.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- Transcription factors that define the epigenome structures and transcriptomes in microglia.Experimental hematology · 2025Review
- Lactobacilli-based postbiotic differentially affects chicken macrophage-like HD11 cells depending on stimulatory lipopolysaccharide dosage.BMC veterinary research · 2025Article
- SUMO operates from a unique long tandem repeat to keep innate immunity in check.Nucleic acids research · 2025Article
- Dual mechanism of inflammation sensing by the hematopoietic progenitor genome.Science advances · 2025Article
- Mutant CEBPA promotes tolerance to inflammatory stress through deficient AP-1 activation.Nature communications · 2025Article
- IRF1 cooperates with ISGF3 or GAF to form innate immune de novo enhancers in macrophages.Science signaling · 2025Article
- Integrative multi-omics analysis of IFNγ-induced macrophages and atherosclerotic plaques reveals macrophage-dependent STAT1-driven transcription in atherosclerosis.Frontiers in immunology · 2025Article
- Liver X Receptors and Inflammatory-Induced C/EBPβ Selectively Cooperate to Control CD38 Transcription.Journal of innate immunity · 2025Article
- IRF8 defines the epigenetic landscape in postnatal microglia, thereby directing their transcriptome programs.Nature immunology · 2024Article
- Transcriptional control of interferon-stimulated genes.The Journal of biological chemistry · 2024Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 4 countries.
Funding
Abstract
The transcription factor (TF) interferon regulatory factor 8 (IRF8) controls both developmental and inflammatory stimulus-inducible genes in macrophages, but the mechanisms underlying these two different functions are largely unknown. One possibility is that these different roles are linked to the ability of IRF8 to bind alternative DNA sequences. We found that IRF8 is recruited to distinct sets of DNA consensus sequences before and after lipopolysaccharide (LPS) stimulation. In resting cells, IRF8 was mainly bound to composite sites together with the master regulator of myeloid development PU.1. Basal IRF8-PU.1 binding maintained the expression of a broad panel of genes essential for macrophage functions (such as microbial recognition and response to purines) and contributed to basal expression of many LPS-inducible genes. After LPS stimulation, increased expression of IRF8, other IRFs, and AP-1 family TFs enabled IRF8 binding to thousands of additional regions containing low-affinity multimerized IRF sites and composite IRF-AP-1 sites, which were not premarked by PU.1 and did not contribute to the basal IRF8 cistrome. While constitutively expressed IRF8-dependent genes contained only sites mediating basal IRF8/PU.1 recruitment, inducible IRF8-dependent genes contained variable combinations of constitutive and inducible sites. Overall, these data show at the genome scale how the same TF can be linked to constitutive and inducible gene regulation via distinct combinations of alternative DNA-binding sites.
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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.