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Series GSE181949 Query DataSets for GSE181949
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.
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
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
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)
GSM5514712 Day 45 H3K4me3 ChIP-seq WT 1
GSM5514713 Day 45 H3K4me3 ChIP-seq WT 2
GSM5514714 Day 45 H3K4me3 ChIP-seq KO 1
This SubSeries is part of SuperSeries:
GSE181951 H3K4 Methylation in β-cells prevents transcriptional downregulation and variance associated with type 2 diabetes.
BioProject PRJNA754033
SRA SRP332226

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Supplementary file Size Download File type/resource
GSE181949_RAW.tar 7.1 Gb (http)(custom) TAR (of BW)
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Raw data are available in SRA
Processed data provided as supplementary file

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