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| Status |
Public on Aug 11, 2022 |
| Title |
H3K4 Methylation in β-cells prevents transcriptional downregulation and variance associated with type 2 diabetes [ChIP-seq] |
| Organisms |
Drosophila melanogaster; Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Insufficient insulin release by β-cells is the primary etiology in type 2 diabetes (T2D) and coincides with impaired expression of genes essential to β-cell function, but drivers of gene expression dysregulation are not well resolved. We find that H3K4me3 peak breadth correlates with gene expression dysregulation in T2D. Using an adult β-cell Dpy30-KO mouse model, we show that global reduction of H3K4 methylation causes downregulation of genes also downregulated in T2D. Reduction of H3K4 methylation increases transcriptional entropy and reduces insulin production and glucose-responsiveness. Depletion of H3K4 methylation causes global dilution of epigenetic complexity but does not generally reduce gene expression – instead, genes related to β-cell function and/or in particular chromatin environments are specifically affected. Our data further suggests that promoter-associated H3K4me1 is sufficient to maintain expression in the absence of H3K4me3. These data implicate dysregulation of H3K4 methylation in destabilizing gene expression and contributing to β-cell dysfunction in T2D.
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| Overall design |
ChIP-seq for 4 histone modifications in 2 replicates from Dpy30-KO or CTRL mouse beta cells with 50% Drosophila S2 cell spike-in
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| Contributor(s) |
Vanderkruk B, Maeshima N, Pasula DJ, An M, Suresh P, Daniel A, McDonald CL, Luciani DS, Hoffman BG |
| Citation(s) |
36912927 |
| |
| Submission date |
Aug 12, 2021 |
| Last update date |
Aug 04, 2023 |
| Contact name |
Brad Hoffman |
| E-mail(s) |
brad.hoffman@ubc.ca
|
| Organization name |
University of British Columbia
|
| Street address |
Room A4-151 950 W28 Ave
|
| City |
Vancouver |
| State/province |
BC |
| ZIP/Postal code |
V5Z 2B3 |
| Country |
Canada |
| |
|
| Platforms (1) |
| GPL25537 |
Illumina NextSeq 500 (Drosophila melanogaster; Mus musculus) |
|
| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE181951 |
H3K4 Methylation in β-cells prevents transcriptional downregulation and variance associated with type 2 diabetes. |
|
| Relations |
| BioProject |
PRJNA754033 |
| SRA |
SRP332226 |
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