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| Status |
Public on Feb 23, 2023 |
| Title |
The Hdc GC box is critical for Hdc gene transcription and histamine-mediated anaphylaxis [CUT&Tag] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
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.
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| |
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| Overall design |
H3K27ac Histone modifications in WT and Hdc GC box KO BMMCs, in triplicate, using Illumina NovaSEQ6000 platform
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/36804390/
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| |
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| Contributor(s) |
Li Y, Gao J, Zhao D, Huang H |
| Citation(s) |
36804390 |
| |
| Submission date |
Jan 20, 2023 |
| Last update date |
Oct 06, 2023 |
| Contact name |
HUA HUANG |
| E-mail(s) |
huangh@njhealth.org
|
| Phone |
3033981281
|
| Organization name |
National Jewish Health
|
| Department |
Immunology and Genomic Medicine
|
| Lab |
Huang lab
|
| Street address |
1400 Jackson street, K511
|
| City |
Denver |
| State/province |
Colorado |
| ZIP/Postal code |
80206 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE223388 |
The Hdc GC box is critical for Hdc gene transcription and histamine-mediated anaphylaxis |
|
| Relations |
| BioProject |
PRJNA925914 |
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