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The Hdc GC box is critical for Hdc gene transcription and histamine-mediated anaphylaxis [ATAC-Seq]

ABSTRACT: The Hdc GC box is critical for Hdc gene transcription and histamine-mediated anaphylaxis [ATAC-Seq]

PROVIDER: PRJNA925913 | ENA |

REPOSITORIES: ENA

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The Hdc GC box is critical for Hdc gene transcription and histamine-mediated anaphylaxis [ATAC-Seq]

Project description:Histamine 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. We sought to investigate how enhancers regulate Hdc gene transcription and histamine synthesis in resting conditions and in a mouse model of anaphylaxis. H3K27 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 using CRISPR deletion. Deletion of the GC box, which binds to zinc finger transcription factors, in the proximal Hdc enhancer, reduced Hdc gene transcription and histamine synthesis in the 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. Our results demonstrate that the 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.

2023-02-23 | GSE223387 | GEO

The Hdc GC box is critical for Hdc gene transcription and histamine-mediated anaphylaxis [CUT&Tag]

2023-02-23 | GSE223386 | GEO

The Hdc GC box is critical for Hdc gene transcription and histamine-mediated anaphylaxis

Project description:The Hdc GC box is critical for Hdc gene transcription and histamine-mediated anaphylaxis

| PRJNA925912 | ENA

The Hdc GC box is critical for Hdc gene transcription and histamine-mediated anaphylaxis [CUT&Tag]

Project description:The Hdc GC box is critical for Hdc gene transcription and histamine-mediated anaphylaxis [CUT&Tag]

| PRJNA925914 | ENA

HDC/histamine signaling axis drives macrophage reprogramming to promote angiogenesis in the hindlimb ischemia mice

Project description:Histamine is catalyzed by histidine decarboxylase (HDC), which plays important roles in many physiological and pathological processes, but its role in angiogenesis has not been thoroughly clarified. Here we report that HDC is highly expressed in Ly6C+macrophages, rather than in endothelial cells using Hdc-GFP transgenic mice with hindlimb ischemia (HLI) mouse model. Given the whole-process promoting effect of macrophages on angiogenesis, a cluster of HDC+CXCR2+ macrophages have been identified by single-cell sequencing technology in ischemic tissue. The inactivation of HDC leads to a lack of histamine and pro-angiogenic factor production in macrophages, inducing a harsh inflammatory microenvironment that is not conducive to the interaction between macrophages and endothelial cells. Moreover, HA-DA@histamine hydrogel has been designed and demonstrated to safely treat ischemic injury by modulating inflammation and angiogenesis. These data highlight the critical roles of HDC/histamine signaling in macrophage differentiation, angiogenesis, and muscle regeneration in the early stage of HLI.

2024-08-02 | GSE273730 | GEO

The Hdc GC box is critical for Hdc gene transcription and histamine-mediated anaphylaxis

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-02-23 | GSE223388 | GEO

Gene expression data from 1 year old Hdc+/+ and Hdc-/- stomach.

Project description:Histamine defeciency result to hypertrophic gastropathy in the stomach. We use gene array to distover the major cause of stomach lesion in Hdc-/-. Tesult shows that chronic inflammation and dysregulation of macrophage functions are the major trigger for hypertrophic gastropathy in Hdc--/- stomach.

2022-09-14 | GSE213293 | GEO

Smoking-induced Reprogramming of Histamine Metabolism Genes in the Human Small Airway Epithelium

Project description:Smoking is associated with increased airway histamine responsiveness and elevated histamine levels. Transcript levels of histidine decarboxylase (HDC; histamine synthesis) and histamine N-methyltransferase (HNMT; histamine degradation) were evaluated in small airway epithelial (SAE) cells obtained from smokers or non-smokers. Histamine+ SAE cells increased in smokers compared to nonsmokers (p< 0.03). HDC transcript levels were elevated in smokers compared with non-smokers when comparing both bulk RNA from SAE (p< 0.03) and single cell HDC transcripts in mast cells (p<10-6). Elevated HDC transcript levels in mast cells corre-lated with elevated IL33 transcript levels in smoker SAE basal cells, and elevated transcript levels of the IL33 receptor, IL1RL1, in mast cells. In contrast to HDC, transcript levels of HNMT were decreased (p<10-4) in smoker SAE. Significant decreases in HNMT transcript levels were found broadly across SAE differentiated cell types. An in vitro SAE culture model treated with cigarette smoke extract reduced HNMT transcript levels (p<0.05). Together, the data suggests that smoking results in an accumulation of mast cells, elevated expression of histamine-synthesizing mast cell HDC, and a decrease in histamine-degrading HNMT transcript levels broadly in the epithelium. These smoking induced changes are likely contributors to elevated histamine levels in the airways of smokers.

2020-08-03 | GSE154136 | GEO

Gene expression profile at single cell level of totoal peritoneal cells from WT and HDC KO mouse

Project description:Histamine is required for full differentiation of macrophage. We used single cell RNA sequencing(sc-RNA seq) to characterize the impairment of macrophage differentiation in HDC KO at molecular level.

2023-10-30 | GSE232834 | GEO

HDC/histamine signaling axis drives macrophage reprogramming to promote angiogenesis in the hindlimb ischemia mice

Project description:HDC/histamine signaling axis drives macrophage reprogramming to promote angiogenesis in the hindlimb ischemia mice

| PRJNA1142941 | ENA