ArticleThe Journal of allergy and clinical immunology2018
The transcription factors GATA2 and microphthalmia-associated transcription factor regulate Hdc gene expression in mast cells and are required for IgE/mast cell-mediated anaphylaxis.
Article in The Journal of allergy and clinical immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- Integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement, migration and neuroinflammatory signalling.Frontiers in immunology · 2022Trial
- Transcriptional Regulation of Mouse Mast Cell Differentiation and the Role of Human Lung Mast Cells in Airway Inflammation.Immunological reviews · 2025Review
- Inactivation of cofilin-1 in Mcpt5-Cre-nf-Cfl1Frontiers in immunology · 2025Article
- Article
- Identifying potential pathogenesis and immune infiltration in diabetic foot ulcers using bioinformatics and in vitro analyses.BMC medical genomics · 2023Article
- The Hdc GC box is critical for Hdc gene transcription and histamine-mediated anaphylaxis.The Journal of allergy and clinical immunology · 2023Article
- Influence of Genetics on the Response to Omalizumab in Patients with Severe Uncontrolled Asthma with an Allergic Phenotype.International journal of molecular sciences · 2023Observational
- Article
- MITF Downregulation Induces Death in Human Mast Cell Leukemia Cells and Impairs IgE-Dependent Degranulation.International journal of molecular sciences · 2023Article
- FLI1 Regulates Histamine Decarboxylase Expression to Control Inflammation Signaling and Leukemia Progression.Journal of inflammation research · 2023Article
- MRGPRX2 signaling involves the Lysyl-tRNA synthetase and MITF pathway.Frontiers in immunology · 2023Article
- ELK4 exerts opposite roles in cytokine/chemokine production and degranulation in activated mast cells.Frontiers in immunology · 2023Article
- New Mechanistic Advances in FcεRI-Mast Cell-Mediated Allergic Signaling.Clinical reviews in allergy & immunology · 2022Review
- Anti-Allergic Effects ofAntioxidants (Basel, Switzerland) · 2021Article
- Article
- Article
- Nanoparticles Displaying Allergen and Siglec-8 Ligands Suppress IgE-FcεRI-Mediated Anaphylaxis and Desensitize Mast Cells to Subsequent Antigen Challenge.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Anaphylaxis: Focus on Transcription Factor Activity.International journal of molecular sciences · 2021Review
- GATA2 regulates mast cell identity and responsiveness to antigenic stimulation by promoting chromatin remodeling at super-enhancers.Nature communications · 2021Article
- The underestimated role of the microphthalmia-associated transcription factor (MiTF) in normal and pathological haematopoiesis.Cell & bioscience · 2021Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundHistamine is a critical mediator of IgE/mast cell-mediated anaphylaxis. Histamine is synthesized by decarboxylating the amino acid histidine, a reaction catalyzed by the histidine decarboxylase (Hdc) gene-encoded enzyme HDC. However, regulation of the Hdc gene in mast cells is poorly understood.
objectiveWe sought to investigate the in vivo regulation of IgE/mast cell-mediated anaphylaxis by the transcription factors GATA2 and microphthalmia-associated transcription factor (MITF) and the mechanisms by which GATA2 and MITF regulate Hdc gene expression in mouse and human mast cells.
methodsMice deficient in the transcription factors Gata2, aryl hydrocarbon receptor (Ahr), aryl hydrocarbon receptor repressor (Ahrr), or basic helix-loop-helix family member E40 (Bhlhe40) were assessed for anaphylactic reactions. Chromatin immunoprecipitation sequencing analysis identified putative Hdc enhancers. Luciferase reporter transcription assay confirmed enhancer activities of putative enhancers in the Hdc gene. The short hairpin RNA knockdown approach was used to determine the role of MITF in regulating mouse and human HDC gene expression.
resultsConnective tissue mast cell-specific Gata2-deficient mice did not have IgE/mast cell-mediated anaphylaxis. GATA2 induced the expression of Mitf, Ahr, Ahrr, and Bhlhe40 in mast cells. MITF, but not AHR, AHRR, or BHLHE40, was required for anaphylaxis. MITF bound to an enhancer located 8.8 kb upstream of the transcription start site of the Hdc gene and directed enhancer activity. MITF overexpression largely restored Hdc gene expression in the Gata2-deficient mast cells. In the human mast cell line LAD2, MITF was required for the HDC gene expression and histamine synthesis.
conclusionThe transcription factors GATA2 and MITF regulate Hdc gene expression in mast cells and are required for IgE/mast cell-mediated anaphylaxis.
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