ArticleThe Journal of biological chemistry2011
Positive regulatory domain I (PRDM1) and IRF8/PU.1 counter-regulate MHC class II transactivator (CIITA) expression during dendritic cell maturation.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 58 citations in OpenAlex.
- Dynamic regulation of H3K9 modifications in cancer: pathogenesis and targeted therapies.Biomarker research · 2026Review
- Review
- Class II Major Histocompatibility Complex Transactivator (CIITA): A Master MHC-II Regulator Impacting Cancer and Beyond.Journal of immunotherapy and precision oncology · 2026Review
- A beneficial environment promotes immune resilience through epigenetic regulation.Science advances · 2026Article
- Transcription Factor Blimp-1: A Central Regulator of Oxidative Stress and Metabolic Reprogramming in Chronic Inflammatory Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Machine Learning-Directed Conversion of Glioblastoma Cells to Dendritic Cell-Like Antigen-Presenting Cells as Cancer Immunotherapy.Cancer immunology research · 2024Article
- ETS Transcription Factors in Immune Cells and Immune-Related Diseases.International journal of molecular sciences · 2024Review
- Transcription Factor Activity Regulating Macrophage Heterogeneity during Skin Wound Healing.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- IRF8-mutant B cell lymphoma evades immunity through a CD74-dependent deregulation of antigen processing and presentation in MHCII complexes.Science advances · 2024Article
- Identification of antigen-presentation related B cells as a key player in Crohn's disease using single-cell dissecting, hdWGCNA, and deep learning.Clinical and experimental medicine · 2023Article
- The Murine MHC Class II Super EnhancerJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- Mononuclear phagocyte regulation by the transcription factor Blimp-1 in health and disease.Immunology · 2020Review
- NonO Is a Novel Co-factor of PRDM1 and Regulates Inflammatory Response in Monocyte Derived-Dendritic Cells.Frontiers in immunology · 2020Article
- Chromatin Architecture as an Essential Determinant of Dendritic Cell Function.Frontiers in immunology · 2019Review
- Overexpression of B-cell lymphoma 6 alters gene expression profile in a myeloma cell line and is associated with decreased DNA damage response.Cancer science · 2017Article
- Development of potent class II transactivator gene delivery systems capable of inducing de novo MHC II expression in human cells, in vitro and ex vivo.Gene therapy · 2017Article
- Langerhans Cells-Programmed by the Epidermis.Frontiers in immunology · 2017Review
- Relevance of Interferon Regulatory Factor-8 Expression in Myeloid-Tumor Interactions.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2016Review
- SLE-associated risk factors affect DC function.Immunological reviews · 2016Review
- Role of PU.1 in MHC Class II Expression via CIITA Transcription in Plasmacytoid Dendritic Cells.PloS one · 2016Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Dendritic cells (DCs) are key mediators of immune function through robust and tightly regulated presentation of antigen in the context of the MHC Class II. MHC Class II expression is controlled by the transactivator CIITA. CIITA expression in conventional DCs is uniquely dependent on an uncharacterized myeloid cell-specific promoter, CIITApI. We now identify in vivo the promoter structure and factors regulating CIITApI. In immature DCs transcription requires binding of PU.1, IRF8, NFκB, and Sp1 to the promoter. PU.1 binds independently at one site and in a required heterodimer with IRF8 at a composite element. DCs from IRF8-null mice have an unoccupied CIITApI promoter that can be rescued by reconstitution with IRF8 in vitro. Furthermore, mutation of either PU.1 site or the IFR8 site inhibits transcriptional activation. In vivo footprinting and chromatin immunoprecipitation reveals that DC maturation induces complete disassociation of the bound activators paralleled by recruitment of PRDM1/Blimp-1 to the promoter. PRDM1 is a transcriptional repressor with essential roles in B cells, T cells, NK cells, and DCs. We show that PRDM1 co-repressors, G9a and HDAC2, are recruited to CIITApI, leading to a loss of histone acetylation and acquisition of histone H3K9 dimethylation and heterochromatin protein 1γ (HP1γ). PRDM1 binding also blocks IRF8-mediated activation dependent on the PU.1/IRF composite element. Together these findings reveal the mechanisms regulating CIITA and, thus, antigen presentation in DCs, demonstrating that PRDM1 and IRF8/PU.1 counter-regulate expression. The activity of PRDM1 in silencing all three cell type-specific CIITA promoters places it as a central regulator of antigen presentation.
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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.