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| Status |
Public on Feb 14, 2022 |
| Title |
Angioplasty induces epigenomic remodeling in injured arteries |
| Organism |
Rattus norvegicus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Neointimal hyperplasia (IH) is a primary etiology of stenotic vascular diseases. It is perpetuated principally by smooth muscle cell proliferation. Epigenome-scale studies concerning IH have been confined to in vitro models, and the IH-underlying epigenetic mechanisms remain poorly understood. The current study has integrated information from in vivo epigenomic mapping, conditional knockout, gene transfer and pharmacology in rodent models of IH. The data from injured (IH-prone) rat arteries revealed a surge of genomewide occupancy by H3K27me3, a gene repression mark. This was unexpected in the traditional view of prevailing post-injury gene activation rather than repression. Further analysis illustrated a shift of H3K27me3 enrichment to anti-proliferative genes, from pro-proliferative genes where gene activation mark H3K27ac instead accumulated. In accordance, H3K27ac and its reader BRD4 co-enriched at Ezh2 governing its expression. Moreover, H3K27me3 writer EZH2 positively regulated another recently identified pro-IH chromatin modulator UHRF1. Thus, results unravel injury-induced loci-specific H3K27me3 redistribution in the epigenomic landscape entailing BRD4->EZH2->UHRF1 hierarchical regulations, and may guide translation to treat IH given that these players are pharmaceutical targets.
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| Overall design |
ChIPseq was performed on injured and uninjured rats for 4 histone markers.
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| Contributor(s) |
Guo LW, Webb A, Gulcin Ozer H |
| Citation(s) |
35169042 |
| Submission date |
Jan 25, 2022 |
| Last update date |
Mar 15, 2022 |
| Contact name |
Amy Hite |
| Organization name |
The Ohio State University
|
| Department |
Biomedical Informatics
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| Street address |
1800 Cannon Drive 250 Lincoln Tower
|
| City |
Columbus |
| State/province |
OH - Ohio |
| ZIP/Postal code |
43210 |
| Country |
USA |
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| Platforms (1) |
| GPL20084 |
Illumina NextSeq 500 (Rattus norvegicus) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA800429 |
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