ArticleThe Journal of allergy and clinical immunology2023
The Hdc GC box is critical for Hdc gene transcription and histamine-mediated anaphylaxis.
Article in The Journal of allergy and clinical immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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Who cites it
6 citing papers in PubMed, 5 citations in OpenAlex.
- Histidine alleviates Hashimoto's thyroiditis via the neutrophil extracellular traps-NF-κB signaling pathway.Scientific reports · 2026Article
- The potential role of aberrant microglial synaptic pruning in the neurodevelopmental pathogenesis of tourette syndrome.Frontiers in neuroscience · 2026Review
- Toll-Interacting Protein Down-Regulation by Cigarette Smoke Exposure Impairs Human Lung Defense against Influenza A Virus Infection.The American journal of pathology · 2025Article
- Transcriptional Regulation of Mouse Mast Cell Differentiation and the Role of Human Lung Mast Cells in Airway Inflammation.Immunological reviews · 2025Review
- Genes Selectively Expressed in Rat Organs.Current genomics · 2024Article
- Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundHistamine is a critical mediator of anaphylaxis, a neurotransmitter, and a regulator of gastric acid secretion. Histidine decarboxylase is a rate-limiting enzyme for histamine synthesis. However, in vivo regulation of Hdc, the gene that encodes histidine decarboxylase, is poorly understood.
objectiveWe sought to investigate how enhancers regulate Hdc gene transcription and histamine synthesis in resting conditions and in a mouse model of anaphylaxis.
methodsH3K27 acetylation histone modification and chromatin accessibility were used to identify candidate enhancers. The enhancer activity of candidate enhancers was measured in a reporter gene assay, and the function enhancers were validated by CRISPR deletion.
resultsDeletion of the GC box, which binds to zinc finger transcription factors, in the proximal Hdc enhancer reduced Hdc gene transcription and histamine synthesis in mouse and human mast cell lines. Mast cells, basophils, brain cells, and stomach cells from GC box-deficient mice transcribed the Hdc gene much less than similar cells from wild-type mice, and Hdc GC box-deficient mice failed to develop anaphylaxis.
conclusionThe HDC GC box within the proximal enhancer in the mouse and human HDC gene is essential for Hdc gene transcription, histamine synthesis, and histamine-mediated anaphylaxis in vitro and in vivo.
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Registered trials
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