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| Status |
Public on Oct 18, 2023 |
| Title |
Splenic CD43- B cells exhibit DNA hypomethylation specifically at repetitive elements compared to CD43+ cells |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by array
|
| Summary |
EZH2 is a histone methyltransferase that deposits H3K27me2/3 in heterochromatin and it is misregulated in tumorigenesis. Inhibition of heterochromatin can induce viral mimicry in cancer cells, where upregulated repetitive elements are detected by cytosolic pattern recognition receptors (PRRs) to activate inflammatory signaling. Here we demonstrate that EZH2 inhibitors stimulate inflammation and immune self-recognition of resting splenic B cells. We generated a PRR loss-of-function mouse model called RIC with mutations in Rigi, Ifih1 (MDA5), and Cgas. In both WT and RIC mutant B cells, EZH2 inhibition caused loss of H3K27me3 at repetitive elements and upregulated their expression. However, expression of inflammatory chemokines in B cells was interrupted by the RIC mutations. Furthermore, recruitment of cytotoxic T cells and neutrophils in response to EZH2 inhibition was blocked in RIC mutants preserving viability of B cells. This study demonstrates a pharmacologically induced mechanism of inflammation that causes self-recognition and B cell death.
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| Overall design |
Bisulphite converted DNA from the 12 samples were hybridised to the Illumina Infinium 285k mouse methylation BeadChip.
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| Contributor(s) |
Dick FA, Kim SJ |
| Citation(s) |
37934086 |
| |
| Submission date |
Apr 13, 2023 |
| Last update date |
Jan 17, 2024 |
| Contact name |
Frederick Andrew Dick |
| E-mail(s) |
fdick@uwo.ca
|
| Organization name |
Western University
|
| Department |
Pathology
|
| Lab |
A4-VRL LRCP
|
| Street address |
790 Commissioners Road E
|
| City |
London |
| State/province |
ON |
| ZIP/Postal code |
N6A 4L6 |
| Country |
Canada |
| |
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| Platforms (1) |
| GPL30650 |
Infinium Mouse Methylation BeadChip |
|
| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE198232 |
Cytosolic pattern recognition receptors respond to EZH2-inhibition induced viral mimicry response that eliminates splenic B cells |
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| Relations |
| BioProject |
PRJNA955287 |
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